S48.01 - The postsynaptic 5-HT1A-receptor and its role for cognitive functions in mice

Abstract

Schizophrenia is often accompanied by cognitive dysfunctions. Post-mortem and in vivo studies have revealed increased cortical 5-HT1A-receptor density and it was assumed that 5-HT1A-receptor active drugs could enhance cognition. Moreover, partial 5-HT1A-receptor agonists positively affected verbal memory in schizophrenic patients. However, the role of the 5-HT1A-receptor for cognition has not been fully clarified.

Recently, we have introduced transgenic mice overexpressing the 5-HT1A-receptor postsynaptically in the cortex and hippocampus. Function of the surplus receptors was verified by receptor activation with the agonist 8-OH-DPAT.

In this study we further investigated the role of postsynaptic 5-HT1A-receptors for cognition. Therefore, our mice were tested in the inhibitory avoidance, Morris water maze, and hole-board habituation task. Moreover, the effects of low and high doses of 8-OH-DPAT were examined in the inhibitory avoidance task.

Our transgenic mice showed no overall cognitive deficit. As a tendency, inhibitory avoidance retention was impaired in transgenic mice compared to wild-type controls. Both genotypes showed similar spatial learning abilities in the Morris water maze and habituated to the hole-board in a comparable manner. Anterograde amnesia induced by 8-OH-DPAT was in transgenic mice already apparent in a third of the dose used for wild-type mice. Retrograde amnesia could not be triggered.

Since the transgenic mice show untreated a rather normal behaviour, we assume that they possess compensatory mechanisms. However, after activation of the postsynaptic 5-HT1A-receptors the differences between wild-type and transgenic mice became more clear. Hence, our findings suggest that the cortical and hippocampal 5-HT1A-receptors play rather a modulatory role in learning.