Cross state-dependency of learning between 5-HT1A and/or 5-HT7 receptor agonists and muscimol in the mouse dorsal hippocampus

Abstract

Background: Dysfunction of the serotonergic and GABAergic systems in cognitive disorders has been revealed. Understanding the neurobiological mechanisms of drug-associated learning and memory formation may help treatment of cognitive disorders. Aims: The aim of the present study was to investigate: 1) 8-OH-DPAT (5-HT1A agonist), AS19 (5-HT7 agonist) and muscimol (GABA-A agonist) on memory retrieval and state of memory, 2) cross state-dependent learning between 8-OH-DPAT and/or AS19 and muscimol. Methods: The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated, and all drugs were microinjected into the intended sites of injection. A single-trial step-down inhibitory avoidance task was used for the evaluation of memory retrieval and state of memory. Results: Post-training and/or pre-test 8-OH-DPAT, AS19 and muscimol induced amnesia. Pre-test microinjection of the same doses of 8-OH-DPAT, AS19 and muscimol reversed the post-training 8-OH-DPAT-, AS19- and muscimol-induced amnesia, respectively. This event has been named state-dependent learning (SDL). The amnesia induced by 8-OH-DPAT was reversed by muscimol and induced 8-OH-DPAT SDL. The amnesia induced by muscimol was reversed by 8-OH-DPAT and induced muscimol SDL. The amnesia induced by AS19 was reversed by muscimol and induced AS19 SDL. The amnesia induced by muscimol was reversed by AS19 and induced muscimol SDL. Pre-test administration of a selective GABA-A receptor antagonist, bicuculline, 5 min before muscimol, 8-OH-DPAT and AS19 dose-dependently inhibited muscimol-, 8-OH-DPAT- and AS19-induced SDL, respectively. Conclusions: The results strongly revealed a cross SDL among 8-OH-DPAT and/or AS19 and muscimol in the dorsal hippocampal CA1 regions.