LAUSR

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 &mgr;g/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 &mgr;g/mouse). Furthermore, the pre‐test microinjection of muscimol (0.025 and 0.05 &mgr;g/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 &mgr;g/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 &mgr;g/mouse), 5 min before the administration of muscimol (0.1 &mgr;g/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 &mgr;g/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. HighlightsACPA and/or muscimol induced amnesia and also state‐dependent learning (SDL).Cross SDL occurred between ACPA and muscimol in the mouse dorsal hippocampus.Intra‐CA1 microinjection of bicuculline dose‐dependently inhibited muscimol‐induced SDL.Intra‐CA1 microinjection of bicuculline dose‐dependently inhibited ACPA‐induced SDL.