Cross state-dependency of learning between arachidonylcyclopropylamide (ACPA) and muscimol in the mouse dorsal hippocampus

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Abstract

The aim of the present study was to examine cross state-dependent learning between ACPA (a selective cannabinoid CB1 receptor agonist) and muscimol (a selective GABAA receptor agonist) in the step-down inhibitory avoidance learning task. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated, and all drugs were microinjected into the intended sites of injection.

Post-training and/or pre-test administration of ACPA (1 and 2 ng/mouse) dose-dependently induced amnesia. Pre-test microinjection of the same doses of ACPA reversed the post-training ACPA-induced amnesia. This event has been named ACPA state-dependent learning (SDL).

Post-training and/or pre-test microinjection of muscimol (0.05 and 0.1 μg/mouse) dose-dependently induced amnesia. Pre-test administration of the same doses of muscimol reversed the post-training muscimol-induced amnesia, suggesting muscimol SDL.

The amnesia induced by post-training administration of ACPA was reversed by pre-test administration of muscimol (0.05 and 0.1 μg/mouse). Furthermore, the pre-test microinjection of muscimol (0.025 and 0.05 μg/mouse) with an ineffective dose of ACPA (0.5 ng/mouse) significantly restored memory retrieval and induced ACPA SDL.

In another series of experiments, the amnesia induced by post-training administration of muscimol was reversed by pre-test administration of ACPA (1 and 2 ng/mouse). Moreover, pre-test microinjection of ACPA (0.5 and 1 ng/mouse) with an ineffective dose of muscimol (0.025 μg/mouse) significantly restored memory retrieval and induced muscimol SDL.

It is important to note that pre-test intra-CA1 injection of a selective GABAA receptor antagonist, bicuculline (0.125 and 0.25 μg/mouse), 5 min before the administration of muscimol (0.1 μg/mouse) or ACPA (2 ng/mouse) dose-dependently inhibited muscimol- and ACPA-induced SDL, respectively. Pre-test intra-CA1 administration of bicuculline (0.0625, 0.125 and 0.25 μg/mouse) by itself did not affect memory retention.

In conclusion, the data strongly revealed a cross SDL among ACPA and muscimol in the dorsal hippocampal CA1 regions.

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