B. Approches, techniques et systèmes biologiques
2. Autres méthodes d’exploration cérébrale
2.4. Approche comportementale chez l’animal de laboratoire
L’approche comportementale est une manière d’accéder à l’intégrité des grandes
fonctions contrôlées par le système nerveux central. Certaines fonctions végétatives ne
peuvent pas donner lieu à ce type d’approche. En effet, même si elles sont elles-aussi régies par le système nerveux central, elles peuvent être évaluées soit directement sur les organes en question soit par dosage, le tout générant respectivement, des données cliniques et biochimiques.
Certes, les tests comportementaux sur animaux de laboratoire ne peuvent prétendre tester que des fonctions communes avec l’homme. D’où une certaine prudence à conserver afin de ne pas extrapoler trop hâtivement entre espèces.
2.4.1. Tests comportementaux
Afin d’appréhender de manière objective l’intégrité des fonctions les plus facilement distinguables, elles-mêmes pouvant signer une localisation d’atteinte préférentielle, des tests non invasifs ont donc été développés. Parmi les grandes fonctions pouvant être testées, les tests permettant de détecter des déficiences motrices affectant l’activité locomotrice globale (Openfield) ou la coordination motrice plus fine (Locotronic®), des altérations des centres
de la mémoire spatiale et/ou temporelle, matérialisées chez les rongeurs uniquement par des
altérations des processus d’Apprentissage (Labyrinthe aquatique de Morris, Labyrinthe en Y).
D’autres tests permettent de tester, non plus des fonctions en tant que telles, mais plutôt des manifestations pouvant elles-mêmes signer des altérations fonctionnelles, comme les tests évaluant les niveaux d’anxiété (Test du labyrinthe en croix surélevé, Planche à trous) ou le niveau de dépression (Test de la nage forcée ou Porsolt) des animaux.
Enfin, certains tests tentent de mettre en évidence des altérations du comportement
social (Test du Résident/intrus), mais sont plus complexes à dépouiller et les résultats sont
également plus délicats à interpréter.
2.4.2. Facteurs de variation
Ces tests et ces approches permettent de donner des éléments d’information mais doivent toujours être interprétés avec prudence. En effet, les résultats peuvent être très facilement influencés par différents facteurs, tels l’utilisation des souches génétiques animales différentes (transgéniques, sauvages) (82), leur origine (laboratoire, élevage, fournisseurs), le sexe (83) et les cycles hormonaux (84), l’âge, les facteurs environnementaux différents (luminosité, matériaux utilisés pour la construction des tests, éléments aversifs ou au contraire attractifs, enrichissement du milieu), le type d’administration du composé éventuel à tester (gavage, per os, intraveineuse, intrapéritonéale, intracérébral, …), l’environnement social, la période d’essai (impact de tests effectués précédemment). D’où la nécessité d’être particulièrement rigoureux lors de la mise en place et lors de l’interprétation de ces tests afin de ne pas extrapoler trop rapidement et de façon abusive les résultats obtenus, d’autant plus que l’on ne peut pas mesurer ni leur répétabilité ni leur reproductibilité.
2.4.3. Applications, Intérêts
Ces tests comportementaux sont le plus souvent utilisés en vue de i ) tester une
molécule chimique, pharmacologique, molécule naturelle végétale (85,86) drogue ou toxique (87) ou contaminant alimentaire ou environnemental (88), ii) évaluer la résultante de la
modification d’un gène par utilisation le plus souvent de souches transgéniques chez
lesquelles un gène en particulier a été modifié, ceci permettant parfois de révéler des modèles
animaux de maladies (89), iii) évaluer de grandes fonctions comme la douleur (90). Dans tous les cas, les tests comportementaux viennent apporter un surplus d’information par rapport à d’autres données obtenues par des approches complémentaires.
Dans notre étude, les tests comportementaux ont eu pour but de venir tester un extrait d’origine végétale, administré per os mais par ingestion spontanée, à la dose de 9%, sur souris mâles, afin de rendre compte de la présence éventuelle de fonctions nerveuses centrales atteintes.
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