5-HT1B receptor knock-out mice exhibit increased exploratory activity and enhanced spatial memory performance in the Morris water maze

In an attempt to characterize the contribution of the 5-HT1B receptor to be havior, 5-HT1B knock-out (KO) mice were subjected to a battery of behaviora l paradigms aimed at differentiating various components of cognitive and em otional behaviors. In an object exploration task, wild-type (WT) and 5-HT1B KO mice did not differ in locomotor activity. 5-HT1B KO mice, however, dis played lower thigmotaxis (an index of anxiety) associated with a higher lev el of object exploratory activity, but no genotype differences were observe d in the elevated plus maze. 5-HT1B KO mice also displayed a lack of explor atory habituation. In the spatial version of the Morris water maze, 5-HT1B KO mice showed higher performances in acquisition and transfer test, which was not observed in the visual version of the task. No genotype differences were found in contextual fear conditioning, because both WT and 5-HT1B KO mice were able to remember the context where they had received the aversive stimulus. The deletion of the 5-HT1B receptor, associated with appropriate behavioral paradigms, thus allowed us to dissociate anxiety from response to novelty, and perseverative behavior (lack of habituation) from adaptive behavioral inhibition underlying cognitive flexibility (transfer stage in t he water maze). The deletion of the 5-HT1B receptor did not result in signi ficant developmental plasticities for other major 5-HT receptor types but m ay have influenced other neurotransmission systems. The 5-HT1B receptor may be a key target for serotonin in the modulation of cognitive behavior, par ticularly in situations involving a high cognitive demand.