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The Journal of Neuroscience, July 15, 1999, 19(14):6157-6168

5-HT1B Receptor Knock-Out Mice Exhibit Increased Exploratory Activity and Enhanced Spatial Memory Performance in the Morris Water Maze

Gaël Malleret¹, René Hen², Jean-Louis Guillou¹, Louis Segu¹, and Marie-Christine Buhot¹

¹ Laboratoire de Neurosciences Comportementales et Cognitives, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5807, Université de Bordeaux 1, 33405 Talence cedex, France, and ² Center for Neurobiology and Behavior, Columbia University, New York, New York 10032

In an attempt to characterize the contribution of the 5-HT1B receptor to behavior, 5-HT1B knock-out (KO) mice were subjected to a battery of behavioral paradigms aimed at differentiating various components of cognitive and emotional 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, displayed lower thigmotaxis (an index of anxiety) associated with a higher level of object exploratory activity, but no genotype differences were observed in the elevated plus maze. 5-HT1B KO mice also displayed a lack of exploratory 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 the water maze). The deletion of the 5-HT1B receptor did not result in significant developmental plasticities for other major 5-HT receptor types but may have influenced other neurotransmission systems. The 5-HT1B receptor may be a key target for serotonin in the modulation of cognitive behavior, particularly in situations involving a high cognitive demand.

Key words: knock-out mice; serotonin 1B receptors (5-HT1B); learning and memory; anxiety; Morris water maze; receptor autoradiography

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19146157-12$05.00/0

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