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Naloonai L,b<ary

01Canada Bob+oolI">€qoeIl<l10l;'~'

cccaoaoa

ACQlJ>s;!'onsand D'ecloondes ,}C""SlIuns.1 B'bllOg'a pOlcSeNI(;e&8-anch de$SI;!f\IK:t!Sb,tl I01J.11" ' '' 1'M'1' _l%W~"" sr.O'<'I J'Y.>" ...wt.nq,,~,

0It_~On,.."" OIt....,'I(lo~.,)

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CONDITIONEDIMMUNE~ESPONSI':STO TASTEAJlDENVIR OIIK£IlT AL

A th....i....ublllitt..,jtotil. .. SchoolofGraduate Studiesin part i alfu l f i l l _ llt of the

Depart .e nt ofPayc hology M.. .aorial Uni ve rsityofN_fo u nd lan d

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.+.

fIlaliQnallibfary

. C'"""

AcQuisilionsand

B<bhogfap/'OtSe<v>cesS ranch

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Injectionof cycl ophosph"...id "ICYI , anirnm""{""'I'I" "~ ~'v,' co nj u nc t ion "'itha conditionalstimulu"leS)h" ""'I~'.'h~t1 yI~ ', ' ""hI...."

toproducepavlovi anconditioni n'J. H"",,,v(', ,

1<'1''''' ''

V,lt y"n,h., criticalissueof ",hethe r'.h"'''>neliti''n....l"'''1'"" ".,'" '' 1""' 11'''111·' immuno supp res si"e.. rrec tofCynr counl....r,1(· I " i•• I"'hi" ,"" dy, 'I'"

ef fec t sof CSty p"andpnstCS r .... xpo"ur.. salin"i" ;"' ",,, n,,""•h. ' directionof conditio nediDl.mn.. res po n s e s ..." .•' "",., ,,,, ,,',1"s , n q.,I~' '''''v,' he"",q qlutination n... ction. One hundred and,,,,-' m y:l1" ."I."··ll.,,,, I,·y, ..."

...re ran do mly as si q ne dto a co nd i tio nin'lI"U', ,,""I,," i,, '1"j ' h,".. ,.,,,, ..

cs (saccharin,:lAC)or "distinc tiv...<'nvirnn"",nta lr-s(1'1' -I<i' I.""',, 10"). Fo r someaniOlals,CS exposurecoincid<,dwi thina" I"";"." " ,,1(i.p.1 injectionsofCy(p a i r"d groups)or saJine(" .,Iin"'l ' Olll' '' )' ~''''"'h" '" , Cyin jec t i o ns occuned24 haf t er exposun,totheCS("nl ~,i,""'1'<Jul'''l. Groups werefurtherdi " i de d follO\olinqCSrc exf"' SUI<'suchrh.,t.h.,1101 thean i ll.1ll sin eac h group received ,II' inj",c l-io rlnls"li " .... eo""r,,, y'0 somepn w i o u s reports,both taste and en"iron_nt .,1 ,"S" Ih'll""",.1'·Jl"~1 ...ith inj ectionsof Cy support.aco nd it i o ned i ....urlOsuppf,,~s,,'",,'/II, production ra t he r thanconditioned immu na<>nhanc " ""' n'. This'"'''''Ii,;",,,~l ilMlunosuppressic>noccurredwit ho u t. a mcasur abl" co ndi tH", ,, <f

t. "" ,·

avers ion ,and did rlotarfectCy-induc"d r"duct :ionsin "",i'lht'I·,i".

Als o,injectionsofCy reduc"dfluid consumption7~h, "u'.n' " ~Il10, lat er. These findinqs ar e inc o n s i s ten t"';thsOIIf' r:urr"nt interpre tatio nso(condition.. d i....un..re s pon s e s and." .. <>X"..i",,<:1 in termsofsi"' ult a nflOUS and seq u e n t ial conditionin'l f" "",,,,-o,, , o:II.

( i i )

(9)

ACIl.owl .dOJ··· t .

I~'..r' .""th is d<>'oll in Sorpte_ rpf1989andl,nUlIo<Iit.• ...f".i...".d~,.hll ~' ...·n nhthee".,..pt. i onofabnut.4 _ tawo. k ,.,...ininqun..~tht.o.i ,it....p, _ .-.arly4~a r .later.and on It,...:ono""r. I ••io n.Ihope>torid ory.elf01 i tonceandlo rall.

Ilhvlf","ly.. . . ..th.. n"YO<l'. (Oft.heeu ended~.. i.nce.c~it_nt..

,tOO~"pp>ft...r"lonq ovel_d.. e.

FJU t.. I'dliket.ot.han k II<lrvinlit..... .. fo rinlth,tinqory in U'''' ''t inthisa. e a ofinvfl'.ti9ati on,"'nd-arei-e><>r u nti y .for Jnt, oo "".n'l..,to"rad...u.su pervisor.GerardHa .t i n . A.pecia l

"..."torr.rd forloll'I1v ln<l_ hi .intere s t . q..id.~ .and

""Ppo:>tI P<lalonqtt\flway.Ibled"catinq_ ontheint ric aci...of

"' ., ,.,,;-,,, 1"Ond i tionl"'Jtheory.leir .. a....ring _ tha t.theLoIafs .i ght

'''K.'

dily.. in.. no thc.< rSt a nleyc..p.andId)eo..nt.l... .hO... .ofhis

~:::: :::"'~~-:,.:~~:.;~io:~~itX>dyti 1O"s, Ihopethat.0".da yIcan I.."..ldal solik..to t.han k ray t.woc . - it.t _lIlberl.Mark U"ld " , ,10dCollo l yn1/,11 1.." to.th.. i.init.ial...vi oflIy th""i.

1""l>Usa).oilS ...11asfOIt.ha l rCOIlIIIIfInt.st.hatshaped th..(lnal

PIOO", :L I"hould..1"0t.h a nk Karkforin t.. o d..cin9"'" tothe Tuesday

:~::~ ~..:~k"yc.owd t.ha t.becameaninc. e oos inq1 yl"'PO.taot part01Illy ransofth ilro...ar ch_r l!cond uct.edat theHea lth scien c "s Cl!nul! ani... llabo.ato.,y . . ...d"0I....t.end .yapP'8'Clati on tolIte n ...tin and0 ••LoInkaHu"alor al 1"",inq_ aCCe SS tothe i requip_ nt and(acilit.i ... . AI.oo(t.h..IIl!dt.h sc i e nce. cent.r... I_ ldiiketo 'h,~n"Or,IIodJl Lal .on(0.trerassist.a nceIn9"tt1n9_ acqu a i ..ted ..iththepersonsandp.<>Ces se..""'Ployedbyt.heDepart_ fit of 1_..l>Oloq y.

1... indebt eato thesu pport. .t.afl o(the Depa .,t..eflt01 I'sycl'IoOl oqyoUicefo rt.hoti ras s i sta nce a10nqtheway~""'ur.... n lor 'Wtt.inq_ th..nec... .a.yTA·S.andBr"ndol lor jUllplnqinand

~:a~::~ ~

..

qthe f1.nalp. od uc t.ion o( t.hl " th", , "whileIre "idedin

P.!o'sot...lu ... nk.t.oMa.i l ynandShe l l .y10 .lJ.teni nqco .y

t. ials~ndt.i buLIlt.l count.lesst1 _". Idou btt.hat.I_ ldl\a ....

~:;7:: ;~':':',hisI' )~twi t_ tt.heaidof"l>Cl'I'q ood li"t.e ne r· .·

(Jli)

(10)

Titl.. Fa" ....

Ack nowled" ...nta Tabl e ofco n t e nts

Listof figures•.• • Li s t of app"ndlc..s .•.• •.•

Co ndi tion i n"i""" u ne re s pons.. s •• . Co ndition..d ilMlunos uppression.

Cond i t io ne d iIUlUnoenhllnc.. ""'nt••. . Po s s ible sources ofop posi nq re s pons..s.•...

Inj..cti on re') l"", ••..• Aasoc ia tiveeree, SUlI\lTlar y andhypot hes.. s ••••

Subj..cU ••••

Ap p a r a t us a nd ma terla la•• . • ..• • • . . • • • •.•

PhaseI,Co mh t i oninq.• • •.. •. .•.• Pha".. 2, CSR... posuro •• .•

Pha s e 3, Euthan asiaand bl ood colle ctio n •. •. . . seru",preparatio"and p..1ssivehemaqqJuti""I.ion.

Immuneresponse•• • • ••••• ••• •_ Fl ui d consumption .

(iV}

(11)

J.? l c:"" 'l 'ti''''i n'/••••

1.??Ir:""'litiuni n 'JD" y.I••• • 1.7.1 .1c:"ndi tionino/O..y-I:••

-1.J.J.1Ct>n di'_i'JIl, n 'JDa y.l••

1./:.1 p"'...""ntl i tion i nq •••••

1.7.1 .1I''''l t condit i o "in'llldy-I.•. 1.J.l.Jf'''''I.o''ondil;Onin 'l 0'' y-J••••

J.7 .1.I1«.'C~po S "r ()D<ly-I.

J.7.1.7~"(!~I>n" u ,...oay- 2.

P"stc~ pnSU '(!.•• W' ·i'Jh t ch ,InW· ll••..

••••••••• •••••••••• •• ••• •32

• •••• •• •••• ••• •••• •• •• 32

3~

.. 3~

lfl\Jllun c res po ns e •• ••• •• • • • ••• •

~"qu""li"lConditionin q withEnv ;r on"",n ta l

Si mu ltaneouscondit.ionin'l wi th E"nvi r on"", nt al

Fluidconsumpti on.. ... . • S2

T"'ltc aver·sion di s s ociat ionli t er" t ur e •• • •••• ••• •••••• • •S4

IfI\JIl"ncrcspo ns "•••••

S..q\wnt i al cond itioni n')wi t h taste

orodorCS·s .

~i..ult<l".. uus condi tioni n g wi th ta st e

Fl uide<>nsu mption ~6

WL· i 'lht c hanqe s••

C nn ' l sumlll.H y .

(12)

AppendhA•••• •

"'p pe ndi x B••.•

(13)

Jo:~I~";...,,, 1..11[)<,Si' I"show;n qtheT~iJinin'l",nd Te"ti"q

"""IiIi,,"s 10',·"d l ",th...Si~r;~O\lpS.1ndth.,i~

5'1'''1'''''1'''· · ·· ·

'1'...1·1..')

M" .l"I!S EM) Ant. i l>odyTit.. , (10 'l2).11'.1Fur. c t i o n of T, ..ini",!(",,,di lionanrl conrlil ion,, 1Sti~lul\ls(CSITyp".,

A".ll ysi~o( V.H;,' '''''''("NOVA)onth.. P,lSS ;v"

1t"" ' ''I'I I ''I.i natio nAllt i ho dy1'i1.e~s

1'1,,,,,,Bo dywn ; 'lhtbyG~oup('ll ••••·

"",' ly"i " ofVa~idnc e(ANOVAIonWe i gh t Oat..

su."''''''y nf R'''' '''h .... ti .. lE''sw h..'et he CS'' ndl heUS hav.·1""'".Pn ",nl <'d Simulta neously

s"..."y or

lol,."....

HChA~l j cleswhe~ethe CS <lnd th eUS h.lVl't.>e<'Il PresnnlcdScqu..ntia l ly.•... •

(v i i)

(14)

Rando mi za t i onofG~ou ps"it.l1 Anim,' l "'''010<' ,t>y Conditionin'JDa y

"'" a n FluidConsum p tion,",I)o[G~oul'sow',r",y~d,,,"" I th eCond itioningPhas...

",.. "n Fl u i d Consum pt io n (ml ) of {;I<)ul'''Ov'" n"y",j",;n<l theCS R.. exposun' Pflasc••

Anal ys i s ofvar ia nc e(ANOVA)on'['''I'W,lle~Con " " "'pti""

onth..~i)<BaselineDa ye••

Pan . i t ioninq oftheG~oupxInj ectioni"t", ac'ion obt<l i nedOntheSix B<lse lin.. D<lYs

'''''''''''<In_lIe.,l,,Pa in. iseTes t " oftl..,G~ O"px In j<'''ti ""

inter a ctionObtainedonth eSix Basel ine D<ly ".

An<ll y s i s ofVa rianc e(ANOVA)"nFluidCons.,mpti o ""r theThr"9Co nditi on in gD.lys

An a l ysisofvar ia n c e(AI/OVA ) onPI" id Cons" ",p ti ,, n""

Co n ditioni n gDa y One •••

(vii i,

(15)

"".,lys;s"I

v", ;.",,,,,

(AI'IOVA)on f']uid Co"sump tionon ,"""'I,t;""in'lU"y Two.

1',J,'.it.i""in'."I'.h"Cu":<G'·ou!,inte r"etionob t a i ned

""Co ,,<Ii' j " ui "" lloJy...

IIrh.lysi,.ofV.~ei,,",;.,(A NOVA)onFI"idC",n!lumptio nnIl C"" rJitio";"'1UayTh' ... .

I'.'t'.i 'in ";,,qofthe Cue:<G.-oupinteedctionobtain~d onConrJi.jonlt,,)Day Thr"",

'''' .'l y ~i sofV.ui,loc eIANOV A )0" 'rapNat ..rCon!lumption )4h.1ft."Conditioni nq.

1I" ...lysisofV,lridnee(ANOVA )onTapWdter Con!lumption 4ft h .:lUreconditioni nq

P.J"it.;" " i n'lofth..Inj"'ctio n:<Day int. e e<ict.ion oM,'i""'1On timThree1'c-2DdyS••

"'loIlys;"Of vole;anc", (ANOVI\)00Fl u idCon!lu mptionon

(16)

"'Mly~i ~of variane""l"NOVA),>I,Flu "t""''' ''''''I'lion,'"

the rintll.., expo s u l(! (>.Iy... .... . .• .•. .. ... . . . • .• • • ••• • • • • • • ""

Pa rtitio ningofthe eu " xCro llI' i"tt' r.'''tio n.,ut .'; II,,, 1 0"FirstRe e xposlIrcOoly On..

An "ly sis of vari..ne..IANO" " 1 onflui d('o n " "'"I>1.i" n "n the Second/l."cx po s u r "Day.

Partitioningof thl! eu:.xCroupi"t.",,<:1.;OI\ol,t";,,,,tt onIl.el!xpo s ureDay'!'.to•• •• • • ••• ••• ••••••

part i t io nin'lof theCUI! x Groupxnevint." r ., ,,!io n obtainedontheTwoIlel!xpos u r eDays

Analysisofva rianceJANOVA} on Fluid Co n Sllmp t;0 ,")1h af terthe FirstReexpos ureD.,y •• • •

Part it i on ingof theCue xGr o u p;nt..r.l c t. i on,,1I'.l;n.'<1 onthe POstl!xpos uredata ••••••••••• •. ••••

Partit i oningof theCu"Y.Dayin t.e r a ct.ion"t"..l; n''' 1on

theweig h tData .

I"~

(17)

~"I'" ''II"m t....·'

tI'O" '" ' ' I) '''i'1«'ill'l ••n'. ib<" ly '.i',,,~m<Ms" " ,,1

"'l d Y~.,!."r,I,'·ini....-:tj"nofS~l\C1,' <I ~pt"d .,,,<1""0"0,1'1]'.).

I",,,...,,'1,,1In,d"'_"'''' ' o ill')the ,Ii,<.",

i""

{,II I","or:~j,i"'lf'dI,'sl,o ns<o,

(18)

"p p"' n oJi" "

Oo>tllll.. "outlin..of..·-,r h~"t>i"""" "

I' .·.•'...

n'

"ppotnd ."8

toet .. ilt!'dAllOV"tdl>lfOS•••

(19)

fl . O) J" U odu Ct.i on .

~:vi<i",,,;.,forbi.dirc c t i nna lCO'!lnu, n l c a t i onoot""" n thece ntra l /Jervou s "y"t,.,' ",feNS I annthei...."n.."ys t e misprovidl.'dby fa) phys i" I"'l i c " J"tudi.. ".fb Ib<'Mv ioralinf l ue nc es oninonune fun ct i on, .,nll1"1 "ondi'.ionin g para d iq lll!land thei r effect s oniMM.lnQi oqica l

"',"' I.io,, !!. Compl ehensive r('view"of (a ) andfbi ar e beyon dth escope of th i s1~11>(! 1ilndca nbe>found in Ader an d Co he n (19911. Bl a loc k (19 8 ~ .l~~4).fHO'oIn(l 9 'H),"nd Du nn(1989).

Thefirll tat.terapt s tocondit ion animm" no b i o loqicalIe" po n " e ... ,,,bytwoBus a i" n in v e s tigators,I!et.al ' n i ko v andcner rn(192 6. cil ed

in lId"r.19 11lj,," i nqPavlovian condi tioni n g proced ur e s , Pa v lov i anor

<'lassie,' lcondit ion i ng invol ve s the"" "ocia tio nof two "timu liby

""'l "...

n,I,, \ I'r".. "ntllti on ... Tilefi rllt otth..setwost,,,,,,liillcalled

t.llnc9_nd jJJ-~nal_'!til!!YlY.§l_(e S ) . The cs sig n a l s(i.e.•prec e d es )the

""""nd !II ill"l u9,tile \!ll-<;<Qn di tionalst i mu l us (UCS). 11,e ues, as its n"...• illpl i " s . . . li c il S relevant ac t ivityfI:o ..theoutset. TheCS, h"w<'~" ',;s"neulral"(;... it.. lic i t"Il tU ..r..levantacti v it y prior ."il~1'.1; ri"' 1 wit h.h"UCS I. Pav l ov(192 7) SlIowedtbat... pea t e d p"il i nq" of,' cs(...q.,bellIwith a UCS (e.g .•foodlpr od uc eG a new l"" pon,," tot.h..es, a~d~.!l.S_~(ell . in thi s ca s e

".ll ; ~,ll l onl.whic hoccurredin ant i.c ipationoft.heUCS.

lIC't ., l ·n ikovandCha rin pairedth e"c :ra lc ll i ngOr he a t i n "of a

"'tI'lh'"..,.,of skin(CSI wit htilemjoc ercnof a for e i gn.. at .. rla l into

IIll' 1"' ,IIOnl' '' <1I" fqu'n..api 'ls(US). Th ..injectionof th is IMt e ria l

(20)

unconditio nallygive s riseLO anincraaae inpolymoq'h"ml'" !<',1l(I'HNI Ip ukoc.-yt..s. Ht...-athi r t ....ndayr"np".-i ncl,Ih.. an i"" l" u ' ,,,'h" ll exposedtoUeCS alone. PMN'sincr"asec1ftOfll.l I'" "t inq)..wlorn.I>' to62\ five hou rs afterre e x posu retothees. ,'I..,,, IV"I'll,1o'v.'l< 'I ~••l totheCSasaresultof thepilirinqa,

AderandCo h.. n rlH5.198 5)rek indl"c1the int...,,,, In conditionediD",nolo'lY wit htastea"" lBi n nstu di"" inwh i ch.1""i 'l" ''l y fl a vo r e d drinkingsolutionICS) was pdiredwiththoinj<>ction,,'"0 ...•

tox i cdru'l' Thea'lentistypically,butno talways, un" Ih<l ~I><od",,, ,,.

tox i n, theycons u mele s s of that fla vored!Io i lltion. """r.1n,1('"to,' n paireddstron';! immunosupp ress ivedruq, Cy rsee NOl."I ) .wilh co nsulllpt ionofdiU .. .-ent volu..."of a SACsoillt ion, 1'h i .. ".l S1"110....,,1 byanexti nc tiontrialevery third day;th atis,tho SACso l " tion....,,, presented but noinject i onwas 'l iven As expect"d,themoJ' ln i t.lld " "I

co rrel a ted "i th th.. volurroo of SACconsu ...d durin",co nditioni n" . Dori nqthecc u rse ofth eexti ncti o ntri ll l !l , !l0... of th...~ni...ll~<li...I, and IIIOrtal i ty rat es alsotendedtovarydirectly...ith1.1",vol "...•"f SAC sol otlonco n s u med dur i ngcondition ing. Ad e rII 'i "H)hY'~"h" lti~."'1 that these deathsoccur redbecauseof aco ndi ti o ne di ....uno!l "I'P" ·"~iv"

re s po n s e toSAC. Mortal ityth.,n, WdS .lttribu t ",1\,0a =m",o..i~''' 1 l... n<l sySt ".. th a tn."ult<>dfromH' l"'atedfnposu,<:'t.o th .. SAr: es. Wi t h theint."'lrityofthe illJllun",syste,""' M k ..n"d. 'h.. ".·"ni.,ll "...'

(21)

...""....U.ea..., itiotlO!'di - . . respons. t o . USt " CSpairedwi thCy

1_' •

rnl'l"n,1"I;~ 1. In<tl idu al1 yca 'J""dr. t.._feqrad"ally ada pt ed lO drinkth.. lrd••ly A. ."ntofw" ter dur ir>q•n_in periodat the

"....'ti _ <>act>day. There_r e)lrai n inqeo,oditio".whiehdiffered

inltM,j , u"aune " t on One cond itio ni ng day(!),Iy0" (IICondi t ionfod .1nl....I" f" u bqr o up.. CSO. CSI,CS2 .andUSIreeflivoo a.1\SAC ..olut i on CotI"> ",in,p.ti rl'd.,itha50"'9/k9Lp. injfICtionofCy30lIllnlaur;

p)No neo n<lili onPd ani.."h !Gr oupNCIrece .l.YfId piau wa t e r which...

n... ".,ir.. d.,ithCy: .. nd(3) Placebo aniJllalll(Grou p PI rece i ved anJ.p .

;n j•..,tio n of.. n"'l....1vo lu _ ofvehicle 30 "Inafterdr i nki ng SAC

"o luti on. On thefo llowing two daysall an ll.ah_ r"prov id....wit h

"la in....teldUfir>q their15.i n drink inqp"f~nd . Thr ....day . after the I..",uaininqtrial lOoty)1 all a"i. .l ..r~iVf"'Jani.p. inje<,:tionof

"hN'fJrNtblood...11..ISIlBC" I . SIlBC..al-ea bltniqnantiqe nus""" to 1ll;... la t ..cooll_..-.diuedan t i body C"bl pr od uct io n. Thirty_inaftel i_,n,z..t 'on...ach an' &l 1intwo"ubqrOllPllof Cond itioned Ani_ I s Il,;rou!>"..:51 .n<JCSll...eprovidedw,tha SAC..ohl t lO nfor 15_i n and I"'-'n inj...,' ...1with ...U,.,.... "lIli'Cond .ubqroupICSOI.cont rollingfor '''''('ff""'I"01 tr.'ll nlnqwit l>outpr .. lI.. ntinqtM ca.reeerv ee plAin 'Ml"r .1nd .1....11"..injP.<:' t lon . A fi ..al,",ubqr oupIU~ 1wa .prOVided ..ith ....H..r "nd<:y 1.0 as..:.••the UllproducedbyCy (Mer.Colle n.197~1. All"ri...."ni7.,lt.ion . NOllC<:llKlit .io n Pdra t II wellqiv enSAC_flavored wa t e r andinj ected wi t h,al'n...wller ea "Pl a ce bo an1M1' rec..ived wa t e rand

"t>inj<.'ction. Th"••bot hCond i t i onedand Non ("ondlt Jon.. d ani.a l .

(22)

(Groupll CSI . CS7.and NC ) wer(>(>~pos "dt.oS"C .,fl'" i1lUlluniz ,, 'iun.

Gr o upCS 2 was tr eat <'<ili k" GroupCSl, .,nd'_hom'jiv" n.1,,,'<"o n,,1\1«'- sal i ne pairin'lJdayslat.er(Dayb), OnIh..1l; ~lhconsl'f'u ti"",I.,y at ter SRBC innoculation(Day9>.bloodsampl .."_I"nt>',lin,, ".1n,' ti tratedbypea s rvehemaqq lu t.ina t ion ldcs c,- ibed in ",,, tho.l ,, "''''t; ,,n l.

GroupsCSIandCS2rep ' ClI(>nt CS IC"'XPOSUre0" On<' or I.w<>

occa s i o nll att.er ant.iqen Innoc u l a t.ion .showln'] .H ....n'loll " <l Ill,.(' sl'''''''' · ''.

TheAb responseIsameasurab l.. palt.ot th...,;mmll n",-""c l ion' "

pr(tviou,"antiqenu:..t imula t ion, Th ..crit ic a ldl f fe."nCf>inth... ", lesult.sis observedbetween GroupCS O andGr oup sCSI ...",n; 7 . illust. l at i n q the condition.. d eff.. ct .. of aCy inj",,!;on (S" "H'I" '" II.

Condi tio ne d an illlai sthat.",.perlenc.. asin'l ' e ''''l'Osu'.' u, SM'f<>ll ow;''' l antiqentrea tment(GroupCSI )Showed "n"t> respons"th,lt w"s siqnifica n t l ylOWP.lth antha tof placebo ,"s _ II ., ,,No ncm "liti n" ....-i lln iNls, andco ndit i onedani .... ls t.ha l...renot ....poseot."s",.(\:'''''1' CSO) (Acle r•Co hen,197 !>I, Placebo treat... d ...nl...,I~,havin"

exper re nc e dnollMlUnOSUPPl e ss i v et~ea t....nt ,hadthe hi'lht'!It

"I>

IjI'"~

~ncln. tl" " t th.. norlll<ll eeec e rcntoSRBCSinlh"., bs en ,, "0'.,n yp~i " . eapcauretoCy. Anilllais inj ect e d wit.hCy,]tthe ti....orj....nni z "'_i"..

(Gr o u p US)had thelo_st tite rs, illus t r a tin'Jlh"~"ppr,,~,,; v..'·,1....-"."

01Cy On the u'ilct iont.o SROCR. Group NC'""b lit"["Oldno'.<lifl ' "

tree condi tio ne d animals(CSO)who wer"not."expo",'<J1.0 SAC. Th."

"at h qroupshavet iter"lOWQ rthanPl a c e bo animalsr .. flt·" I."th,·

unconditionedresidual i_unosuppr.. s"jve"tr..

"t"

ofCyillj, ·"tf«1<,'i.' y "

eHl ier. Group"NCandCSO ar..t:hnappropriate "ontrol')ro"p".",,,in ,,' wh ich to..valuate t:h .. "tree t:s of""ndi ti o n; n,]andCS , ....xpo " u ,,'.

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FiQ" r.I: He_Qgl"t.inat' n!l'an t ibody t i t .rs_••ur.d/;day••ft . r the injectionofSRSC. NC (n_l0).nonc o ndlt i on.drats;eso (n=10),condition.d.ni"",l. that ....r. notre expo••dtothe CS aft.r ilMlUniu tion:CSI (n_l1) andCS2 (n.9). condi tione d anl lnal sr"..xpo sedtoth eCS on on "ortwo occasion r..spectiv.ly ; US(n.,10) .condition .d anilM.l.

in j • .,t.d ithCyatthe t1_ of1""", ni:at10n...it hSI'lIlC:P (n=1 0).pl ac.bo- t reat"dan imals (ad aptedfrolf! Mer "

Cohe n. 197';) .

(24)

Gr oup.

(25)

",.h."IC init.ial rellOJlts . t.h" n . su ppon: " dth..hypothell18t.hat.pail'in g S... comlu," " •.ion"'i t. hth"inj""'t.i onof...n irrununosup preSllive dru g wou l d .. n;obl,. SII" t.o "l ' cit.an illllluno s u p p rellS iver .. "pon " e"(Ad.. r~coh en, 1'#8'> .p.]8J I.

The s ..II...fi nd i ngshav ebeenreplica t.ed by Roge r s .Re i ch.

suo...andCilrpent.e r(1976) and wa yn eI'.Fla n e l'y . andSi n g e r(1978) 'oIilhv.~r ;().,,,doses andat.dif ff' r ent.tim..saft. e r innoc u liltio n . Oth" l0 olt l"mp'.lltoeonfirm...derandCoh e n's(19 7 ~ 1re su lt. swi.t.hva riant. ll of IheirMlll CprOCf'dure,e .g••Gorc z y nsk i , Ma cRa e. ,J(..nn" d y.19 84~ Kran k ,"acQu.... n.)9aa;l'lilc Qu.. en,siagel .19 a 9 ) ha v..not.been lluccess f u l. Tn..lle invest.i"a t.onlobt. a i nedinllt.eaojco ndit ic ned ill\lllu noe nh olnceme nt.tr-·f\vi r onment.al signals for Cy (" .... Tables6 anoj 7 for.,r"vip", oflit ,""t.hat ha verevea l edCIISthatar..not in the 9,'m<'dire cti o n as t.he URs ). Theinab ility topl'odu c .. cOllsist.. nt CIl".

<lmll'iteusin' J '.h..lla....do" .... ndti _-of-da y para _ t.el' l.illaproblem.

Onefact.or which IMybecontribu tingtoth..se di s c r epa n t repeeee ,U ill CS frolldiff..rencesinbas el i nere s u l t " . Af t.. rre vi ewi ngs .. vera1 studiesithallt><"Co ,"", ..vid ..nt that.not.all":tp<>rilllent.a lpr o t oco ls yi .. ld.. qu!v a\.. ntb;}s(>\in(>effec t s . Cons ..gue n tly . con clud i ng eithe r r"nditionl'd i",",unosuppr"'"lionorimrnu noenh ance_nt. ....yonl ybea funr!ion('f the Ab t ite rsobtaine dfroracon t rol and unp...iredgroups.

FOI ... .. . ple .in Allerand coh..n·s(l9J~1stu dy,Pla c e bogro u p anilllais rcc"iv " d w.. ter p..il'"d 'oIithani. p.injectionof sa li n..du ri n ql.r aininq .. nd s" bsf'quen t ly pr od uc.. a_a n Alle r eer va lueof 7.7. HOlo'9ver.when

!'I.l c Q,"'" nlindSI..g.. 1(1<l89 1 co nd it ionedSalinegr o u panilllah to SAC_

S..lln..dur i ngt uin i n g.the yobt a in .. da....sn...bt tt ..rvalu .. of 4.7. A

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differenc.. of 3.0whenusingth"sa.... <lssay technlq u"C<lnno l r" ..sona blybeattributedto SACal on ... 'rlli sdlff"r e nN.'b<>c0/lll'~<'v"'l IIOl esi g nif i c a nt whe nCy traine d ani..al sare cons tdcrcd, In'!.lcU" """

andS1"'gel'se"pe ri...ne,groupUnpd i redani mals under'lO the "....lu f' n" '-.

SAC_>1411 delay->water->Cy andproducea ....anAbtit.",of J.Q.

He n c e ,wi th in theSameStudy, an i "", ls ""po sedto Cy pn><h'c"

"\1

Iit.{),"

1.7units bel ow Sal in econt rolani.. alswh one v p r ""Jl('ri.. nc"Cy. How.

tnen,isadiffer e nceof3.0pos siblebet...,,,n th.. contro l'1roup"of AderandCohen(197~1andtho seof Mac Queenand Sie y"l (1911qlwh.. u neither group is e"posed to Cyl

"der and Collen's(197~1Pairedani ma l s leceilloone!>;,\.C-';'y pa iring<lS do"'<lc QUe enandSiegel's (1989)Pa i rPdan i ..'l s , th"ilIIh titerval ues,followi ngonere ex pc e u r eto the SAC tast...

"'''I',

,1T1'4.', an d~.l.respect ively. This diff e re nceJIIay beat tribut l"d to .. lnor _thodological va r i ..ti o ns aCrOASlal>orator ie8. Howeve r,wh"ntil.. ,.. , Paiced qr oup ani_Isacecompa r edto th" icresp.,eUvecontIo ]'IH'''p'', twoopposin'lCRsac esuppor ted. With Ade r and Coh"n'shi 'lh bo'He!in""

(P la ce bo " 7.7,No n _c o n d i t i o ned_~.61. they conclude ,1 <;onditi"n,· <!

ilMlunos u pp r e s s ive response to the SACtasteCS. SlnCf'f'M<X!u ,.,...o "n<'l Siegel'" bas elines<lr elow (Salinecontrol· 4. 7 ,Unpa ir ed.. 3. 01, the y sugge. tth<ltSAC controlsa condil_ion<>dilMlunoenhan<;{) ..",".of/II>

prod uct i o n .

Forrllin'lac cu r a t e predictions abo u tthedirectionof theelf firstly re q u ire sreliab l eandre plicab l eba!le U nedat a. Only I_hl'n viI I itbepossibleto clarifythecon tribut io noftilBUl ''' '''"'.0'h..

requlation of illlJlunefu nct. i on .

(27)

~",...,studieshave demonstratooconditionedcompeonsato ry Immu lI()unh~'IC"lIlf'ntto "ignalsforCy-inducedanti genicre activity.

"x,loopl...r.on;zynski.fital •• (19 84 ) foundthattaSteCues pa iredwi t h Cyrj"li nq theti'/ht port i o n of the diurn..l (d.. yti me)cycle n3ultedin c,,"<I,tion,,,1 i.... unos u p p.·esslon.yetpa iringsofthe sa.... stimuli dUJ;C i ng th" d.nkportionofth e cycleyie l d e d either no CRor a conditioned immuHoon h,lnce....nt . ltJ;Ca n k andMa c Oue en(19 8 8) investigatedtheCR to {'nvi ron",.,n t,,1 or dru gstat e cues that signalCyandfounda comp<:' ns"toryCR. The y al s o tested the eUec tsofitt....te cue pre" .. nt.,d in conjunct io nwi thanenv i r o nment alCue. Despite ,j" ""Hl>lt,atin qa si gn ificanttilste evere to», as AdelandCohen(197~) did .In.II'i .... I"...h"re ceiv.. d both CS".theyfound that thecombInation

ad ditioll .tlyck.Greenber'l . and Osachu k (198 6 )ha ve reportoo

"ump<'nll,no ryconditioningto polylnoll inic. po lycytidy l1c IIc1<1 (poly I,C)an t ige nwhe n"",a " u J;Cinq natura lki ll e r(Nit)cell activity of lhe illDlUIlC r eapcnae, tnsum .theseinvest igationsreveala disc[('p.1ncyinCRs...h" n Cy"" rv..sasthe U£1. The focus ofthe

"xp..'ti """ n tproposMl h"re i"onthe co nd itions wh i c h caus eand/or product'the tWO oppo"ingr .. spon" "s tosi gn a l slo r Cy-ind uced i..."no s up p . e S8 i o n .

(1. 4 ) PossiblesoY{CCs of opposingres ponse s . (1_4.1 ) Inl" c t io n r eg ime .

In th i s "'tud y, t..,o.."planatio n" are adva ncedtha tmayaccoun t

(28)

for thediverqent re!!ult!!. Th.. fir!!tis founde<i on"l<>vie wnctil..

li t oratur .. that'ndicat..!! on..!!i q nific"nt Pl o<' P,lt""Iinctln~I"'ellcy.

Ithasbecome appa r e n tth.ltanimal!! who Unt1<'r'l" Ih"'....'I"...n'· ..~llIll' _~

SAC durinqth..t.... t ph",s", ofth" .. KpeTi ....nl"l ,1...

",'1"

"h" .. "V 'Ol' Il""for a conditioned iaununoe n h an cementof J\.b production1<','1" Kr;", k..

MaCQu<>e n .1988;MacQueen..Siegol,1989),..here.. ""n,...,I ...h"

e" per ionc ,the sequenceSRIlC_>S"C_>salin",I'''pl. , y ",·"",1;1'''1",<1 illllllUn 0 5 upp re s s lv.. respo ns e(e .g., Ad ..r .. Cotl"n,1<;J·'~- 191l" I, eff ec t .of in j o c ti o n procedu... .. alon ehav ..al s o b<><>n ..t" ...." to.1 11'...·' outcomesina var i et y of condition, n '!andnon_c ond it , o<\ill 'l """f , "".

wedono tknO'ol.. hy this postre e xpo su r e injection("ai, ,,,,,is ",it;,·,, 1 indp term i ll inq th ..dir ect i o n or the CR.

(197 ~ )freg ile ntl yprod uceaconditiormdsupp ression01i..."n"

re ",cti v it y (see T",b l e61. Fore""'..pl n .Roq er"p, al.11<J·/I" t',lV"

co,,'i n....d the res ult!!of MerandCo llen (l<;J1~,us,nq .,n i'f"nt,,,, ,1 pro t oco l ,and O'Reill y and Exo n (1986) hav "extended lhosc'i "di " 'l"by

!!howi n q '"cy-e enc.n.renee!H. ppr essio noftill"'ellac ti v i l y in

,..o ' !!.

McCoy. Ro x zlll<ln.Mil le r.!lelly.andTitu s{19 ~(',",on du",u'd1 ..xperi_nts thatprov i d eevid enc.. for",on,Jition"di"'u nn'''' ''I''''''''''<>nin Fi !!herr"'ts , Bal b / c ..ic ....and ...it h dej",y s ola l<>n'l..a (,hIM.'...',,, '""

CSandtho us. In alloftlma eexperi _ nt s , .1 salin"inl''':'. i""

'0110-<1 SACCSre e" po su r e . The .. vid.. "c .. supporti"'1 lI,i s

"'1.<,,-

reexpoe uresa lineinjec tionCSRBC_>SAC_>B.llin",is fful>st""li;.l. oeee al s o""i s tfo.- th.. conve r!!e:th"' t15, ttl!) "PI"',....n"" ", ., compensa tor yeRvh .. "th.. s e guenceof 'l1«>nUI islJ",l tflodt.o Sf<OC.>5,0\1:.

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Th~"PI"'iH a nc e or " conditioned illUllunoenha nc.. men ttoan t l g ..nlc:

,..h" I I" n'I " i" ot>"" ,v.,<1 wh" n inv..stigators ha veno tinjectedan ima ls fol l o wi n'l th..SACCS r,*, xpos u rephaseor the exper i men t (e.'J••~ra n t ~ M,,, ,v ,,',,, n .19 98 :MacQue en~Si e ge l.19 8 9 ). Th i s ef fect ha sal s ooo..n r<'porl.",Jwit hHI(cellactivityusi n q poly I,Cant Lqen (Oyctet al., 1'''It. ;solvason,Ghanta,•Hir, ulIa to,19 9 9 ).

Th"impo r t .. ·." .. of injectionprocf><! u rps(ha ndli ng ) perse1s

"uppnn<'<1DythprpsuH sof se ve ral"xper i _n t", . For exampl e .Mar t i n (I Q8 2."~p" ri...nt 21foundthat8sali nein j ec t ion s betweena p<m l.ub iul> ita l_>I.; el phas eandaflavo r_.>pentobarbi t a lcondition ing ph.' !lndidno t extin'lu ;s han associa tionbetwee nhand li n gcuesandthe ini,-"-' tiunorpentobarbital. H<>Wever . whenthenumber of sa li ne injpc ti o n "b"' ...'..th"two ph ase" wa9incre a ge dto 22.Cu n n i ng h a m and Lin.,ll i s(19 9 0 )nbSp'lve<! aleducedassociat i onbetwee n han d lingcue~

an<1 th"in j",,,ti onofpen tobar bit al. Non .co..di t l o ningex pe r i me ntshave .,1" u "tIown tha tinjec tions01sal inealonecan alter tr yptophanlevel s in'd t l!(Hclde r..Huethc r,199 0) ,andind ucea su ppressionof Nil: cell .l<'liv Hy(Ptld.' ,S~ol n i. "t... "'ro ra.1'190).

The"ec ond pos"lbleso urc eofdis c r e panc y is associ a ti v ..bi as in jll\llluneeOfllt1t loni n'l' !l:rank and Mac OUee n(l9 8 6 )andsrecct,Ilra n k.an d Hi n,," n41<)81 )"'''Jq"st that..xt ernal css(s uchasenv i r onmental cu es) IlI00u,~"dl u '1- 0P POS l tl' CRswhileta"teCS"resu ltinagon i s tells wh"n ryt"' h" \1!:.

""c h f'vil1..nc.. sugq..sttl th atpavlo via n con d i t i o ni ng principle s

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rodula t etheeffectsofdrugs(fo r ar<,vi(>W,~""Sil"l"\'lq ll J;Si"'I,'!

.. tal.,19 9 7 1; that is,envi ro mnentalor eontl'x t".ll ,,1'111,'1"I'" '1"" 1 administrationacquire t.he ability 1.0elic i tphy " i"l o '1i ""1 l'Ih'Ih ...

int er actwithdru'l "n"cts, fo rmallY"tf"c t s of,h """,It.., ,....i"... , ant i c ipa t ory comp""sa t ion ;fOl example,the !lubj£,ctwi lh.,hi", '''y,,1 IIOl p lline ad mi nistratio n(a "d it!l "nalql'llic.,n db"h."'(uo.II",',I."iv.' eff"ctsldi llplay s hyper alges ialJl:ran k ,Ilin s o n , 5i"'1"I,1'11111 ,,,HI beh avior alactivation (Hinson 'Sie qel. 19 8) 1f?RS"1'1''''';''',,,Ih, ' dir " c terrec e e ot llledrug. Til" rol"of"nvilun_nt al~i'I ""I"'''1 dr u g admi nistr a tionlias no tbeen consi d "r e d by A<\e l ,1,,<1C"hen. ·I'hoy Ilav"taU "d 10 accounl tor IIII'ina b ilitytupr"9"n tIll" 1.1"'.•, ,'SISf\Cl wit ho ut lIi ..ul lan" o u sly 'livinqexposur e1.0 "nv,root,,·nl.. 1or "<>1"". ,,,,, 1 CS!I. ForAde randCohe n, howe ve r ,I.lle SAC CSpr o v"<l 10tlC'mo'l' sali"nt . per h a psdue topr eexpo sur eto •.hedri n ki " '1 "onl"X1..,,,,,I over sha d owe d any envi ronlllentalCueS thatmayhave1" '('111""~"" 1.. nth.., investigatorsla.q.,II;r a nl<..MaCQue en,19 8 8 jhild Les9h.,llit",'l.i "" '0 con textualcu es, andasaresult, conlext may haveov",~~,,<Jo...,,1III"

tast eCSand yieldl'd "nimmunOt'nll.1"c-" ""''' tof...ll1'"><1",,, ion. An axpl a"a l.iontorthe t""Oop po s i "' l CIIS is th,..,1mo"nt " f habitua t ion1.0th..dri"k i"q sched ul.... "'der<tnrlCoh .. nCIn.,.l'1l1l1 typically 'lavaon..wlffik atIla b ilud lio n tolila dr i nkin'l""h"' lu l""~,,,l.

Theyrepeated lyeapcsedlhea"iltldL to lhedrink ;n' j"ont"xt,,,In,10 co n di tionin q. Un i n t e n t i on all y .t.he CSprl.'expoS Ule~·tf~'C..m"y!I.IV'·

af f ee t e<!conditio"inq10 lh e<Jrin l..in q"onle xt I I.u how~"''''....1'1','11 . CS prea xpo su r a red ucestheSotIi.",,, ..of a"u ",,"dit" "tdlil.y'.n"n" "

intoanassociation. Kelat ive 10ano v l" tasl"''''''. il''',IIU 'XIif<

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",""Xf"'s"dio. ",,",uldloeowors ha d owed by a tas te es. Thislatent inh,b i t i " n"xpld n<H_lonwouldacc ountfortheco nd i tionttd suppression

Tn ," "'O,lIIt forco nflictin'! find i ng s,Krank and"'olcO"" e n(1999) h.w "/"o/JOsuath e lollowin'!lIIOdal (see Fi'lur C 2). Thecolumns

(l ~ t",ll,,..jues ty P" ") re p re s e n tthedualunc o nditi onal effects otey,

h"~hnaus.,.. anda suppressi on or Ab produc t i o n. The rows(l a belledCS 'Yp"s l ,,, pre sen t thetwopoaa IbleCS9, ta s'.eand"nv iron mental CUllS, Til" ty"",ot Cuedel e rmine,the tormof theCR,either l ....unoSUpp' C911i o na,"1ilM unoen hanceme nt . wtlenit ispai r e d withCy.

Whe n ., t., n e cue sorv esas theCSitisassocia t ed lIittl nausea which [." lIlu,,,'s.. ' .l S t",w ers i onleadinqto co nd itio ne d ilMluno s u ppre ssionof AI>pro ducti o n. OnlytWOuce pt10llstoth i s patternexi s t. In3 ot5

".prorilfl(>nls ....acOu""nand 51"qel119 8 9 1 repo rt eda s,a,cfl a vo res ,",uppo rlinqacondit i on.. dilllllUnoe nha nc e men t . Gorcly nski ee.al. (199 4 ) .1IllO r"po rtt><1 cond it i one d imunoe n han celllent,but itliasob s e r v e d in only ]018 elfperi.... ntll. These .Gtudiesar e descri bed {urtlle r inthe ,Iiscussionse c tion . ""ccord inqto Kran kand...acOu""n'smodel(19981.

,-.nosupp r e s si on19strllss· induced...-he r .. the strass isbas edon the '" s w,."'<Hsion . Whe n "nanvir onllent"l orcontextualcuese r vesasthe C1>,It j;lpdi.ed wi t h "suppr e ss i o not Abpr od uc tionle a din ,! to a

(,,~...nSd I.Ory CR.

Th" ,cl"tiv ccontr ibut io n of apa.r ti cula rCSanditt curraspondi n q CM llhoul dC/'ldllqe when one cue is IIIOre salient than the ..,the' . On<>QCtllodot"lte.inq CSsalie n c e isha b i t uati o n. If til ..

envl, omnCllla l es ill !,.eexposedandeeaele sssalientIha nthetaste

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riqure2: Associat.iv ebiasllK>del for dete rm i ll i " q It". dire ctiollof thecOllditiOlloote s po " ,.e (d d " p U '<l1" '10 Kralik "lid "'acOu een .198 8 ) .

(33)

"

+'

~

g

lIJ

~

~

c

0

Hi

"

§

~

t~ f

"0 owe

_" 0 e

... 1Il....

" -"

0."

:~

~0.,

~~'8o _

....~Q.

l

" '

....0.0

g~:

u·'"0 ~

. .

~ +'

~

lIJ U

(34)

CS.then thetaltewillaV"~l h..dow thecon t e xt(,S. 1I.t't'ordinq IIIttl"

lIlOCIel,th i 8 l....dl to animmuno suppr e s siveCR. 11,howr v<'r ,Ill..t" ..I..

CS ilp~ ""x POSed ,the rebyntduciag itsd;Slinc t ;ven"l?lI, Ill" conl,•• t,'S vi I I beCOIl<O1lIQ~"salientand willtesu ltin .1ca"p" n...Hory('II.

fun d ame nt al que, tionni.l ugfrolllthese div<n4ent res u l t "ill wll.'t ceeeeetneetherelativecont~i bu ti o nof eachof thelwoe~.. . lI...""u""

crcond itioningc ..nreecie ineit he ~'::1'1onnencoeonr.Or.1su pp",,,,,j,, ,, ofill\lllu ne function, thepossibilityexist.sthat bothCSs PI<ly ""mp<>t.,.

Ttleaxpe~ieentcond ucted hereassessesilMlune"'Mctivityto bothIyl"-'~

Althoug hthere have been man y~epo n.. 01co nd i t.lo n"'l ilMlunolog ica lresponse .(lora reviewseeAde r "Cohen ,l'l So,; llunn , 19891,the ev i de nce,""""in s inconclusi vewith "''lar dtothedi 'f'Ct jo ll afth.. CR. Several inves t JgatorshaveobtaJnedres ultsSUI'I"..tln',;) condition a d i_ uno suppres a i on of AD pn xlu c t io n le,'1.,/<d.n •coh'm, 197 5; Oorczyr"I kiat er.,1984;Rog e r s et a1.,1976;Waynm"t.11., 197 8 ; 1,yetthe evid llllCII toracoepeneaeor yillllunoen .... n<:1>men lto antiqenicchallenqe also exi"ts(e.g . ,Oycketal . ,I'IS6; (;cu e «yn"k;

et at, 1984~Kr ank'MaCyueen,19BB; Mac Qu e<':< ' Sioqal,I'!B'II. Til.. ' two opposingresponsesoccur is bothim.e restinqandiroport.a nt.:..., sugg e st two re asonsthat JllayLeresponsible fatthe observ<.'<ir<:lIu IL".

Theexperimen tconductedheroexee rneelWOiss ue s . IIIdocs

ti,,,

ty peof cue(tas teor environlllCnt lhaveanerrect0,'the directi ou'~I theCR,and(2 ) h.. veuline injectionsfollowJ.nqCSr.,., x ~ s u r< ·

(35)

affected~ub,.equentilMllne r"action,. ? In .,11 o(the..xpe r i lDent s, tile q r oupe and c"nditlon "u"eda COlIIpositeotthose of "'der andCo ha n 11 \l1~,19l:1~l.Han kand"'a cO u" ""(19881.andMacQue e n and Sieg"l (191:19 );til..pri .... r'/ inve"ti qatorsr"spon,i bl..to r theoppos inqvieV1l, 0t.1l9'tllan til" use ofa limitedn,uDber oftreatlOOntqrcups,th..

l'foc<tdur" " us e d intll"..e studies.for tile ece e part,re pl icatethose us e d by tlloabo veaut.h or s.

(36)

(2 .11 ~

Onehundredandtwe n!.y - fiveexpcrimen t<l ll yn.. iv,·....1<••,lll in"

Consta nc e, Que bec Iwererando"lyas s iq nf'd toindi v idu ,ll "u~p.·"d. ~l st a inle s seeee rwireeag ..s(25elllx20 Cl'lx 18 "Ill). Th...s(>('"" ...". situatedin~ni..ol~ ted:toomtomi n i-mile ext r an eo" " di sr uptin ns . Th,·

colon y :toomwasmainta ined ona12hli'lht_d .u k<'"yel"lOIOO- I~OOh) underst ~ nda ,dfluor escentill u. i na t ionat atempe r ,,! u, "01V -01_7

·C. The ani-Mia.wei'lhi n'l216_264qupo n ani- va l inttl" 1.1h<>r.,! O, Y•

...:rce'liven14 dayll ofha b it. ua t. i o nec thecolo nynX>1Ip' ior'0 lh"

Sta r t ofthe e" perille nt . Cont i n uo useccee..tofood(1""ind R.l! n ... . and tapwa t erwasavailab l eduri nghabi tu<l tio n . Su b jec ts ....ue",d<jhlt.!

eveTy thiTd da y between1400_16 0 0h.the ...ti ... dur in',whi ch .... i ••,1

Oftheor iq in..1125su bj ee ts,120wcreincLud ed inth eLlua I ana lysis . Theddt..fr olllfivean i... re _reotII.itt e d 1><.'C.. ullenon" 0'

toalllless vne eneranylPeasure ofillllllune acti vi t y Wd"V'"' ,, ihl"wl ! ho.. ! prio r an t i'leneXjX>sure.

Cy cl o p hollp h ... id ..wa s pUTcha sedfrollSl qlllaLabor a t.or j<!!J(SI.•

Louis,MOl lind lecon !Jtitut..,dwit.h Inj ec t-a b l e 0.9\l!Jot-onic!Jillin.. ('1 '1

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or ''''CIper 100 0.t ofst e r ilE<...aterl to...concenu,...tlon of 2\(1 gof r:y

')(1'

'>0liltof "al inel . CyclophosphaJlide isusedmedi callyto p'UVOI't cellu larpr o lifera tionne c e ss ar yto lIIOun t I"""un o l o g ical rl"fen"l:(ll l "cll.'" Livinyston, 1990 ; will .anI Farrier ,19891. previou s lIlud ili ll u"inyt.h ls dos ..('>0mq/k 91haveShOlmit to be bel ow the

A0.1\SAC(Sig ....1solution (I9 cot SACper10 00 IIlI of tap

",ateT)ser vedasthe dis ti n c tive flavor cue and",as pre s e n t e d inglass ....lIM bott. les. PI...iq l astubs(4~Clll x 25 ellx 20 CIII \lith_t a l ",ire li dS 'lndhe a t treat edBet...._chip bedding(Hard'olOOd Labs,wa rre nsbu r g, NYI . providedthedi s tincti vaenvironl."'ta l Cue . Thesetubs were loca tedonon""I d "of the colonyrcce ,

She o p red blood col ts(SROCS I fro ..Woodlyn La bs (Guelph, On t ado l, wereusedtosti..ulatetha animalsIlDIDune syst.elQ and ve re ills "" necessal'!c01lJ,lOno n tIn thepa s s i v e hellilgCJlut inatlonreact ion. The y_fapraparedInthe follO"oling1Iil,1Rer:def lbrlna te d blood, hO-.<ltocd tvalue of10 ~ 8 0 ,...as ce n t rif u g edtor to 1I1n andthe supe. natant ...as removed. APPfox llll<lt e ly21111 of"t erH e physio logica l

"alin e",all add ed to the blood ,andthe tube ..., "h akenand centrif uged toranot he r10lIIin.at. ",hich time thesaline /se r ulIllayerwa s rellOved.

Thisproces"

"'a"

repe a t edthreeti mesin order to inllureapUCl'!, da ns <,l y packed, ert nr ocyr.osample. Forin nocu lat i o ns , ...esneecells ... r ... 8uspendedi.nsali n e to aU conc.. nt.r...tion(lml of packedcell . p<:>r 100..I of." li nel. The conc e n t ra tio n us"dintileimmu n eau...y ....as

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10\(101111otpackedcell aper100ml of.,lli."e ). a"l h (''' n<':..,,11,1Iio n ..

wereche c kedto rcone teeent.celldi sper..i.oll us inq ee.. ,,,I,H .I he lllacytomete r pr ocedures. Suspens i o ll"_ re us edwi lh i " ]4h<>1 pre pa r ae Ionandke ptrefd 'ler.. tedwhell 1I0 t ill u.... .

Fo ll"....in g 14 da ysof ha b it u a t i ontothe1.1bclC.n ,,,y, jIoI,H '"1 dep r iva tions("hedu! 1Iwa ll instituted andmai" la in Ad until 24 hI"i,,,I"

th.. coirece.rcn orblood. Th.. re str ict.edw'ltprsChmlu !" prr, v i ' INI anj....rewit hecceasto tap wata r int.hei r-lIus pe n drn1caq e " I'or MImin du rin g the m<>rni"gee e a t en(0'llO- 1130 hi. Anadd i t i o n,l l 10..in,1"""'S"

towaterwasprovided1>9t... n 16 0 0-1 80 0heachday. ~'oIJ ""'i n qRi~ dayllofhab i t u ation toth..waterdeprivati on .eqi ....the con di l innIn. , phas aoftheexperi Ment. boogan.

Thaproce a di nq experi lllllntaldeta il ..da..ceibe....en 01 th..

ellper i _ n t a lcon d itionsasthouqhalla"i lllaiswi th i neach'l, c'UI't",t1 l>e-9ntra ined si lllu lt a ne o u"ly . Toensu rera ndoaoi z atio n ttm .. xpec i- . n t.. ) gro up s wer ein !ac tdis tributed ov e r severalday s suchthut 24 .."i....'IH trcu rfe olll eachof the six ql0Up S'weratr di nedon anyqiVUll d<lYI"" "

Appe nd i x AtOICa de ta il ed rev i..wofth..trai ni n qs!:h(,d ul o l .

p.l.l) Phase1, Co.1d it ioll ing

Eachco nd i t i onin<}trialin v olve-dfo u r d .. ys, Ij;'s..lin " . Conditioni n g. andtwoPo st ,c ond it ioningday". Dur i ngth.. solouldayM

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...cll"ni .... l ...s injectedontwo occ"$ion8. Ba s el in.. daysoccurred24 II priortoCUtl pro "..nt..tionan dprovideda maallu r eof prct"Onditioning tall water oonllulllption. Thenellt day "''' S .. Condit ion ing da y. Fo r the Toln e_cUIIani ... ls (101"'60) a1istinctiueSAC solution ",a s substituted CortapWolt e r duri ngthemorning drinking session. lnv _cue"niuls (H~~OJ",."" re mov edfrolllthei r suspendedca geand placed in thenovel Pl e d 'll a s tubswhe r e the yre ce I v ed tap ...eve rCo r60ein , III I U wara pl " c e din the s"....Pl e d 'l las tub on eachtrialth rouqhout11.11phase s oftile experiment . l_ d i oSta l y followi n gcuaexpo e u re all anillla.ls _fl'injectedi.p ....itheithe r Cy(~Omq/k9 1oroSn equivalentvolu....

of physioloqical sali ne(Bee 'tablel). Ot the 'reete-cueanimal., 20 rece l ved SACpaired "'i t h Cy(SAC~pairedqrou pj,20 rac ..iv9dSAC p.oiled With eertee(S AC~ Sd 1i negroup) .and20 IIlOrereceived SAC paired wi.th eetme [SAC-Unpairedqrou p ). Env_cuean i ...ls ware siJlli la rlydivided andinjected. Twent y .. nilU.h were expo sedto theenvlronllDntoSlcue .1ndreceived an injectionofCy prior to being ret urnedto the i r suspendedceqe fEnv - Pairedqrou p),20 received theenv i r olllDllnt al cue p.:Ii r edwH II iln injectionof ••00i ne fEov_Sa line 'lroup J. and20 othen recei ve dtheenv lron Jlll!nt al cue pa iredwit h aninjectionatearrne (F-nv _Unpaired grouP).

Tile nextd" y WdS the first Postconditioning day (Pc-l)and all

<llnillldisver e qivenace e s a totapwaterfo r60lIlin. Followi ng tap Wolter rellOVa l.rat,.intheSAc-paire d,SAc_s aline, Env_ pa l r ed , and the Env_Saline qroup8 re " .,l v ed ani.p..!'.!li!!.~injec t i on. Rats fr 01ll the

(40)

" .

oroup. t.b. h Subll'I'OIlPI

"""""

<:=l...L..l =.LL..l ~

see-cy w/inj

Sae- Cy

Sac -Un pa ired N· " ! w/inj

N· " ,

"l1nj

env- cv wlinj

env-cv

Env-Unpaired N·", w/inj

N·",

Io// 1n j

ey•cyclophOlph arn !d. . SIISC• •,he .p ca dblood"Ill•. '4cc h ll r in. En v=.n v i r o ","n t. 1W"ta p water. Pc- l. poltconditioningd" y one . Cond .co n d i tioning day. Thre . condi r ionin<;rtrial.

_I'

eh "pl ratadbydxdayl,andtwo r"expolun tri all ...er Ip.olrllt e dby72 h. sRac ...

t.

inj e ctlldint o tilt ,pri o r to thefiu t,butnot the . .cond. R' '' xpoluraday . Under the R.ex po s ure h...dinq,the firstlubgroup(w!tnj lindicate stho . . animals that reeeiv./I.al i n..inje ction"tterSRBCin<.oCu lat i o n andCS lI.expoeu r l. Conver•• ly. Ilni lNll.who ateno tgivenaninjlcti on_tter CSR....xpo s u... Ilrein dic<lt edby (w/o)lu bg r o u"l. In.11gr oup.n•20. Subgroup.alwa y.consis t of0" .halfof the/Mi n9'-ouP .population (e.9.,Sae -Cy w/in j,na10 ).

(41)

SAC_Unl'air..d and t.ho Bnv_unp airedgroups rec ervee an injection of£l ('>0 III<j/ktj lfollowinqtapw.. t.e r rellOv..l. GroupsSAC-Unp a ireddndenv- Unpairedalo 24 II control sto'Ul s essth e unconditionederreceeofCy inj'o<:ti o ns . OnddyPc-I,ran inth"PairedandS..lineqrcupswere ini o ct edwithaerrneI" eeTa ble II. AsecondPostCOnd itioningday (1'<:_21occu rred48hatter the. condition ing tria l andprov id e d a . ,asure of tapwa t e rccnaueprIcnby the 'Jnpairedqroupon tho day aHertheir Cy in jac t i o ns . This setoffour days lllasa line , Co ndition inq,Pc_I,andpc - 2)co nsti tu te s onecomplete conditioning tllal. Each an illalwallsubjacttothre eco n d i tio ni ng trial s, sep.lratedby sixday intervalsto minim iz ..the possibilityof cu.u l a t lve dru g eUee ts (Ca labresi,parks.1'18!i ,Stland• Liew,HilO). Daysl~b, 1.12,andlJ-1B ...r ..condi tion ingper iods I,2,and3, res pec tivel y(see Tabl.. A-Ifor ade t a il ed outlineof each subject'S tre.. t_nt schodule).

Day19 ...rkedthe end of three condi tion ing trilla for all anilllaia and thflbeginningofa 14dayrecove ryperiod . Dur ingcees e days, anilM IIIreee rveetheirwaterbot t lefor 60Illinin thair ho...

ceqe .. t t.hesa ....timeas On the cue exposured..ys(0!130-1130h).

wate r walla'lainpresentedfor 30 lIlinbetween16 00 -IBOOh.

(2.3.2 1 Phase ,. csRf!eHlQSU (£

EolChCSR... poJlure trialconsistedotth r e e dol.ys, IlaselinQ,cue aee x po s u r e,olnda POsteJ:posyre da y. The scatexpcaureday provided '"

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.... as uB Iof t.ap....au u · conscaptrcnfoll o....ingcue 1I....xl'O" u "" , OnIl" yIII rat.s wer e in noc ulat ed wi t.hani.p. inject.ionof ,~1\(v/v}th neo ....esneeSRBCsolut.ion(2ml / k.g; app ro x illlat.el y3"lOB celllt'.11t,..'...."n 0830·0900 h.. AnillMl\$inj e c t.ed Wit.hSPBCS wereret.utnadto t.h..i, suspend e dcag e. At. 0930h, ..ni 1llals~erereexl'Oll edtothO >I,U"" cue UII"dduring condi tioning. 'raeee -cue .. nil\loll srl'l' ei vad SACfin bO .. in whil eEnv·c ue /lni mah wero trans feredtothe Plex i g liiS tub ll ,lncl rec e iv edtap wate rfor 60 Ii n . ThUll, inaccordiln ce withtto..p"' >l"'<l"ro ' of Ad"r/lndCohen (1915) , lran kand Ma cQ ue en (198 111, (Illd Hilc Ouepnand Siege l(19 89), iloi ... 18_re presented withthe irn's pect i v" l'U"Onlh...

da y of an t i g enicchaU en ge ;thisconstit utesthefirst Ree"po"u ", 'd.lY.

Forhalf of thoanilllillsin all groupll, an Lp.

aauns

m ]..ction(2 Ill/kg1fol lowed cue lleo"po su re ; theot.h en did no trec ..iv lJ"lIill i ne injecti on fol lowingRaa x posu r e(Ult e rtoTable II. CUORt>O"POlIlH O....,11.

repeated12hla t.e r(DayJlj,aswerethe saline in j l!Ct. i on " ,bUIthe SRBC innoculations werenot r"p9i1t ed. Fr.... aCCf'!lIS to....ater ....all retns eeeed 24 h prior tothe bloodassaytoenureado q ua t ebl<...,,\

Volume fo rthe illUlluneassay .

t2. 3 . 3j P" a " ..J!l!'utha na siaandBloodCo l l ec ti o n

8100dsamp l es (approdlllil te l y4eel were obt ainedtnreedilY~

fol lowin g th.. second Reexposu r edily. Begi nni nqilt113 0_ 12JO II, aniDlill1_reeeecvee fromthe ireceecago'}l,d <lne ll th er.izedwith pent.o bacbi tal(65~/kgl . Ratswere the ntranspo rte'd insus pcn<l <'d

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...i."r.a9"ato anotheraection of thefa ci li t y. Blood...acolhlcted ...ith .1cin.H...cpunc t ureunde rs ..lIi - a s e pt i c cond itions usin"a ';cc sylin'!.. and18 G n....dl .."'he n subjectsno longerrespondedto e .-od"latetailpinch (about12 Olin after injection of pentobarbita l!.

Ani-.al s....H ..then i _diat..ly lIacrificedvia anlop. inj e c t ionof.. n ,,<Jditional6'; OI"/k"ofpentob.. rbital.

(2 . 4 ) s ...rull lIre p.. rat1on..nd PallSive Heugqlutin.. ti.on WllOle Dlood oDt..inedtr oll anesthetizedr..tswe8 placedinto 8terileheparin-rin sedtest tubesand centrifu"edat 600 x " tor 20 min. Thetop !!erUIl la ye r... a then nrewn off with pa8 teu r pipet te8and place din anoth..r te8t.tulletobecentr ifu"Oldagain, therebyrelllOvin"

,,,'-.anycel l" frollthe aeru.. .08 possible. Whe nthe lIerull...11 chla r• .. fterhavin" been c'lIlt rifu gedtwice,it "'''11 relllOVed...ndheatedin a

ra t lIera...asthen placedin.0...11...hi chconta ined an equal aDlOunt of

ecttoe, Thasol ut i onwas atir r edand 100 microlit,-ellwa sre ll)Ove d and

d.. positedin anothe rwellwhic h .0180co ntai ne d 100mi c coli t rasof saline. A"ai n, thi ll mixture was stirredand 100lIic rol i tr es dr a wn off; this processwa srepeated until12sucbseria l dilutions hadbeen prepared, Fiftymicrolitresof a 10\ SRBC !!olutionwallthenadded to eachofthetwelv e _lls. The - U swere then coveredwith parafil m ,lnd re raainedsta tio nar y fo r fo u r hourswllil e thelIellWl9"lutlnatlon

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Each ra t ' sSer a ...all prep.lredin du p liColt e.~ndlOc"n«1by' ....' obs e r ve r a ...hoIo/(lr euna...are of the ,ats '1"OupdlllOiqlllk>,H. "1"11"

in t e rs a mpl e correlationcoe ff i c i e n t s(PeilrSOtlproduc tOk_'U' corr e l at ion1for obse r v e rs A alldBwere II(II",I ) ..O.n4,

I' "

.0 0[1

,,, ,,t

(r(U91 .0.930,P<.0 0 11, res (X!'Cti vely Ontwo1dti n'l "",K'hof110

reece tena, Additi o na lly, the interrater,,.'tn · LMiOll'""" 1rki.,..1w., "

jr( lJ 9 )·O,916 , p< .00 lJ.

'rn ree ty [lP.of data are reported, Abti te rs ,fl ui <l ''' '' "a'''''I 'ti"" , and body ...ights. An a Ly li isof va ri a n c e (AlfllVAIproced ures"",It'tl~,..l to access di f f e r ene" s alDOnq ""peri_nt ll ) andcont ro l ",oup " . WI",,, ,I sign if i cantdifterence... ObtainedNeWllliln-~.. uls _t hod oj ." Ilil'["

cOllp.. ri son"... sused(Fe r g us o n ,19 761. Si q nitica n tthr e "-...,,V in t era c t i o ns ...re anillyzedinac c ordancewith U,epU>C<ldUIUII dm'''liI ...,j by P;:e p pe l and Zedeck (1989) . Theacc eptabl e si g n i l i"" ncu I,we:I", all analyses...as set at .05.

(45)

( j.11IJIUllu"".k.osponse

CUntfiHVtoprec onc e pt i o ns underlvinq th i s ex"" t i lDent,th .. only tVI'" ofcond it.oninqobeor vecwa s a suppressionof illllO-un'l activityand this sU!'Pr ...ee ron w,n equallystron<J to eithercs type. Theuse of injP.<:tions duri nqH.exposUrl! also hadno effect,

Table1sho"" th ..i. .mraq" passiveh<>IIlM~'l' l u t i llat io lltit"cfo c ,",lch of thl!three<jro"psofTaste-cueandr.llv~cueanil'lla18. Rats

<>x pe rlt>rw i llqthe ""qucneeS"'C _>Cv 01'Env ->cy Oil thre.. eorKti tio ni nq tIialsdisplayedthe lowest Ab titers"'h <>n tested withsubs eq ue ntcue

",.... pn"ur e. A 2x1x2(Cue [s ....C orEnv lx Group[pa i r ed ,un pe rrec, orSal!nelx Injection (S al ine orNo Salin'll)ANOV.... revealed a .. iqnilicant ",,".neff ectofGroup1[ 42. 1091.,10. 12,P<.001). All other co",par illon..wer eno tai q llif i c ant Ip s>.41)Is.... Table 31. Ne wraall.Ke u lspairwi s e tests ,Fer'luson, 1916) Onthe.... anaofthe si'flli!icant_ inertoee re""alod thatthe Fa i r e d group hadrelia.bly 10000r....btitn rsthan boththe Salinetq-8.89,F.99P.1111-4. 201 ,lnd thl!Unpair e d ('I.,3.41,f.9S(2,111)· 2,8 0 ) qroups. 'rhe Unp.url!dljroupalso hadreliably lower All e reersth a n the Salineqroup tq·~.411,f. 9 9(2,Ill )·3 ,1 01, 'flu"dift el: e ncebet_n the Ab titersof thePail:ed gr o up andthe Unpai redqroup is clea revi d e n ceof N>llditionlld immun o s up p r e s s i on ,and thedi f f e r e nc e betweentheunpaired 'l'ouP,l ndtheSalineqrouprerreev e th.,.r"!!Iidu aluncond i tional eff ect of threeCvinjections. The s e result!!l are notco nsiltentwith the

(46)

He n (t8 ! M) ADtibody Ti h r (10 921 &11.. PUDc t Io ..or 1'r..in1ll9 Co n di t ioft nd Colldl U on &l Bti.ulull (ell Type

Gro u p

CStype

Tast.e(Sac )

Unpain>d

Sh Ly ani/l\alswen' an i 'lnedvoeachCStype . rdi l llu.

Unpair<>d. and Sal in.. qroups co ns istedof20ratspl'r cup. ThpIn jP' ''.i"n fa c t.o rwasotIlittedin thi stable becaus e itsinc lusionofle,,>dno additiona l inforlllat i o n(seeTable 3 ANOVAI .

(47)

scur ce of variation

Ke••gIIl t. i n .t. i oD Ant. i body

sum of Me a n

Squares square

Cua xGroup Inject..ion CuexInj Grou pxInj Cu ..XGIxloj

~'aClor9are cuea2,Grou p(Gt)aJ, and Injection(tn j)a2.

(48)

reportsofIIr a n kand MacQuee n (1988)and 1t"'C'Qu e e n dndSi"q"l (1911ql insofarasnoneottheseinve s t i<ja ton. ob t ...ined iuunOfluppre"sion to

Thefiveani llal s thatwere not innocul a tCdwithSRBC"butWJ.'ro oth" rw i " "tr " atedasSali neqrouprats ,produc edM!titersofZ""O. Thi s de monst ratestha". with the te ch ni qu e employed here, puwioua antigenexperifmeeisnece89a r yi ftheim.:mn.. syst....is tobe

(3.2) Fluid Con" umptio n

SAC ...ndta p " ...terconeueptIon "",re recordedtothe n.. aI .."ttp nth of a mlfor.. achda yof the ..xper i _ nt . Me a n SAC cons uooptio n forth..

Taste _c uerats and_a ntap"at..rcons umptionfor the t:nv-cu.. rau. h prel"mtedforthe'daysoteac hCondit ioni ng tr-i al inTab l oB- 1 , TableB-2 s.."nea rizesthefluidconsumptiondata frolltho CSRee_posu' o phas eofthe.."per-i....nt. Th.. Baseline,Conditionin'l , ReeJi po surc , and Postcondi tionin <jdataaleana l yz edsep a r-atelysince eecn ofthuse d<ly..

provide aIlleasur-eoff'lui d cons umpt iont.hatd .. "c r-i bcs<lpar ti c u la r featur eofanan i mal ' straining schedule. Each tVpe ofda yis di sculls.. dunder- individualsub- headings tha t couespond chrono logicall yto th eorder oftheexpelilOOn t .

Insummar y, fluidccnsurept.Io nfor-all<lni lMhdidno tdit f o , on Baseli neda ysbut apro nouncedSAC ave rs ion wa"evident inSAc_pa i r ed ani lD/llBfo11O'<i'in9asingleSAC _>CypeLrjnq , Thisaversio n pP.!8ist<><1

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cverbothCSllee_po" ufO' da ya. 110aversion,..as observedin eev-serree dn i...]. to ta p ",,!It,er l rathe r,con,umpt ioo reaa i nad consistent throuqlloutallphasesottheexperi_nt. Post c o ndi t ion in q data .uqife . t ed th"tinj e c t i c.nsotCy reduced flu idconsulll ption24h, but not 46 h, later. Dur Lnq the Reexp<'>s u r e phase the SAC-Pairedq"oup sho~an dversionto the fla vo r cue, but theEn v_cu eutsdi d not show any red uctionin ta pve eer con"umption ",hil e inthe novel Plexi g las t.ubs. Themanipu li> t i o n of fo llowi ng CSIle e" poll"""",it h an injectionofsaline didnotaff ec t fluid consumpt io n .

A 2x)x2x6(Cue x GroupIlInjection _ Day (wit hi n factor] ) I.NOVAof Balleli nefluidconsulhptionr''lVeal eda significanteffectover D<lY8l!':l~, ~40 )..10 .14 ,P<.OOIJ , anda Group xInjection int e raction[[(2,lOBI-).18, P0(.04~](seeTab l eB- )I. The DdY effactindicat elthatSODe fl uctuationinta p ",at e r co ns ullption occ u " n ,dthro ugho uttheellperilllent. Thesi"thBas el ine day used in theanalysis illa_asurlloffluid cons umption 48 h afterthesecond Reexpollur e dilY,and illaBase line mea s u r e to theexte ntthat1t pr cced ,.. the nextexperillle nt al IIil.nipuldtion (immune allsay lby24 h.

Analy s i"oftheGroup x Injectionint8 uc t 10n di d. notre vearany

"ystellldtic ef fectsoftheinjec tio nHlgi_ on fluid coneue peIcn 24 h priortoeachotthethreeconditioningdaysandthe twoR__pos u"..

day s. Th~limpl"mainIIffect s IntheGroupxInjec t i on

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inte rac tion ne presented in TableB-4 and thesubseq ue ntNewlla n _ l(>ul ~ cOlllpa risons are pr es e nte d inTa bl eB·'). fha t .111'lroups

_u.

comp<arablein terlll8 of fluidconsumptionpriorto fluid.,,_

presentat ionsU'l'l e ststhat alle niJD.lh hadrecove redfroll the unco nditio na ler rect e ofthe dl uq.

(3 . 2. 2 1 ~

AS su_rizedin Table8_1 , SACconsu"'Ptionby the th ... 'IIOUPS of SAC_cueIIni ....b 'olli Scompa ra bleonthetirst Cond itioninqday. OY."

the courseof conditio n i n q .cons u mptionofSAC bySAC_S ali ne.:Ind SAC_

Unpai redi1nilllalsincrease dandIItab iliz..d (M• 22.2 .1). but consu lllpt iondecreased forSAC_pa n e d iloni aa l s fol lowin qa sin'll ..

injection of Cy(M• 7.9",II. The thre<'!qro upsofEn v _c uera t... did no t show any d<jnifican tch a nqe ll in tap water co nsum p t i on(M•Il.A mIl overthe three cond ition ingtriah. A 2 .. 3 .. 2 II 3(Cue .. r.,o"I' ..Injec tio n..Day,withinfacto rIIANOVA ofCond iti o ni nq day fl"id eonsumption re vealeda si<jnifica ntCue II Gro up II Dayint..raction [f ( 4.

216) •30.46. P<.0011IseeT"' b l eB-6 ) . Subsequent ana l y s e s""""

ba s ed on 2 x J x 2 (cue xGrou p IIInjection)A.I10VAsofeachefth ...

eneee Conditionin<jdays (Ke p pel ,19B2).

p.2.2.1 )Condi tioningDay_l

A lIi q nifica nteffect of Cue [l(l. lOBI. 47.22, P<.00I[Io,r,]8 ob ta i nedonConditioningOay _l Illee reeteB~71. NO Other~Iffert'"~"s

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_r" lII'lniticant (ps ».')0). This cue e !tactreUeetsgU!lI.tel"

consump tionofII.nov,,1SAC flavored solutionIII..16. 8 JIll) relative to plaintap .. ater 1M~11.1 _I)in a distinctenvr rceeem.

(l.2 . 2 . 2 1~ondi ti on i ngDdy_2

Asiqnifica ntcuelrGI"OUp intel"act ionIf(2. 108)..31.61,P<.

.001 ]was Obtained on conditioningDay-2(6e " Table 8-8]. Subsequent analysisofth elIh ple Nineffectsrev e a l ed a si'lnific antdifferflnce oot'ofCCntheen r e e group" (paired.un pa i l"e d , andSoJii n e ) whenSACwas

theCueIf(? 216)~101.45 .P<..001](see Table B-'ll . Newma n-I':e\l ls

cOIDpar isonsof theIlea ns (refel"toI"OWCo nd _2of Table8- 1)l"eveoJled tnatthe SAc-pa iredgroup consumedreliably less SACth"neither the SAC-Saline(q~19.06, F.9 913,57)..4.281orthe SAC-Unpairedqr'oup (q..15. 16 ,F.99 (2,51)..3.16). SAC-Unpai redani lDo11salsocons u med l"e li a b l yle s s SACth","SAC-Sa lineanilllolis1q"3.89,F. '.!9(2,'H)..

3.1b ). The ilecomparisonllindicatethatthe SAC-Pairedani_Isha d an av e r s i o n to SAC based on a sin'lleinjectionotCy a nCo nd i tio n ing Oay- I.andthatthe SAC_Unpaired ra u had a weak SACaversi o n despitethe 24h intervalseparati ngtheil"l1xp<:>sUl"e to SAC andthein jectionof Cy . ThLIIef f ect W/ISnot obsel"ved intheSAC_unpairedanillldlsdUl"ing subsequentexposu retoSAC onCondi t ioninqoay-Jandaeeapesure Day -2 , t>ut w"s evidentOnR...xpo s u r eDay -I. TheinstabilityandlIla'lnitudeof ttle aversionlIIiIy reflectsome SeilS itizationbyttl'"unpairedanimalsto thetasteCue. Nosi g nif ic a n t differences exhted in the tapwa t e r

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conllu~tionof env-e ceanilDab On Conditioni"qDay_l(llee Tabl ..0-91 ref e r to row Cond _2ofTa ble8-1 torthemean s ).

(3.2.2.3)Conditionino D.ly_3

Asignif ica n tCue" Groupin"..ea" t i o n 1r(2.109)*116.)1>.1'<

.0011>lall ob t a inedon ConditioningDoly-3 tluidconsu" ptionl""eTabl. , 8- 10 ) . Analysifl ofthesia>ple maineffec ts rcveeieeasi'lnitlcant diften . nc e betweenthe paiel!d.Unp<ti eed.andSaliloegroups ",henSAl'

>laS theCue(E I 2 .2161.. 241.43.P <.0 0 1 )but not><hen tho enyieo n_ nt was tho cue(See 'rable 8-11 ). N.. """,n-Jleuls compiuisonllIII thl>lIolIanlllr e t ertorOWCo nd-)of Ta ble8_1)revealedthatthe SAC_

pa i r ed qr o u pconsumed reliablylellSSAC thaneith.. r the SAC-Unp.lir"d (Q•27.49,F.9 9 (3. 57) -4. 28 1 orthe SAC-Saline '1r ou p4'1• 26.9", F.99 (1. ~1)..3.16). The SAC-Un p a lc edandSAC_S alin" qr o u psdidnot dif f e rIq ...499, F. 9 ~(2,~1)• 2.83). Thes e dataMeol<Jdi tional ev idenc efora con ditionedtallta aversion in the SAC_P"iredani""ll".

The threegroup " of tnY-Cue ani. . ll1dr ank"olllpilra b l e allDun t s of tap wat erwhe th er orno t it>laS followedbyaninjectionorCyfreterto row Cond-3of Tabl eB-1) . That(lui d conllumpt i o ll doe ll not ditte[

betweenEnv- Pa i r e d ,tnv_ Un pa i r e d . andfnv-Saline ra u lIt1gq est"tn.. t fluidconsumpt ion doe " not re ve al .. ny conditioninqeltectlito envieonlOOnta lcues. Condition i ngit reveajedbV the conditionedAb ereer data for eev-cceolnilldlllthat wallde scribedearlier.

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1).2 . 31 ~~~n_diti on in9 1).2. ).11~.9llCondi t ioni ~

postconditioningOay_1(pc-I)cef'ns toth..day i _ d i a tely followinqa co nd i ti o n i ng day;th us. there aceth r ee pc-Iday s . A2 x ).II2x)leue 11Gr o u p x Inject ion 11Day l ...ithi nfa c t o rl ) AHOVA of fluid co n s u!lPt i on 2<1h aftercondi tio ni ng n.vealeda significant eff ec tofGro u p[[(2,lOBI•3t. ~2 ,P<.0011. NOother dif fer e nc e s wele obtain edIPlI>.0 9)(secTableB-12). subs eq ue n t.NeWlll.ln-l!.euls anal yee 8 ofthecc.bi nedpc-ldays delllOn5tc a t e dth atthe paired <;Iroup 1M•l~ . l_1)dra nkre liablylU8 tap ...atel than eithe rthe Unpaired (M- IB. 8_I I('I.8.1B, 1".9913,111)· 4. 201 crthe Saline group 1M

·1 8.&111 1('I. B.40,F.~ 9(2,111 1. 3. 70). Thefluid consullptionof th esat

me

andthe unpai redq roup did not differ('I...377 .F.9 ';(2.

1111"2.8 0). These comparison8 indicatethat injectio:>n sof Cyred uc e

fluid consu llPtion2(h later.

Tho secondPost conditioning da y (Pc_2)occ u rre d 4B h after th e Conditioningday. A2113"2"3 (Cue"Groupx Inject i o n x Day ("ithinfactor IIAHOVAofPc_2flu ideo ns u lllpt ion revealed a signif i can tInjection"Dayinterac tion[[ P .216) •3.13. P<.02';) and CIOUP [[(2,lOB)..24.] 1, P-c.00 1 )effect[see Table8··1)).

tIe ...n-Jouhdnalysee on thecrcup effllc tshO>iedthat the Unpaired

g.oup(M.. 14.0; Ill) drank reliablylessfluid tha n either the Paired

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