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

• Published in: Pharmacology, biochemistry and behavior Vol. 163; pp. 66 - 73
• Main Authors: Jafari-Sabet, Majid, Karimi, Amir-Mohammad
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2017
• Subjects: ACPA; Animals; Arachidonic Acids - pharmacology; Bicuculline; Bicuculline - administration & dosage; Dorsal hippocampus; Dose-Response Relationship, Drug; Hippocampus - drug effects; Learning; Male; Mice; Microinjections; Mouse; Muscimol; Muscimol - pharmacology; State-dependent learning; Mouse; Muscimol; ACPA; State-dependent learning; Bicuculline; Dorsal hippocampus
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2017.10.005

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 2ng/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 0.1μg/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 0.1μg/mouse). Furthermore, the pre-test microinjection of muscimol (0.025 and 0.05μg/mouse) with an ineffective dose of ACPA (0.5ng/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 2ng/mouse). Moreover, pre-test microinjection of ACPA (0.5 and 1ng/mouse) with an ineffective dose of muscimol (0.025μg/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 0.25μg/mouse), 5min before the administration of muscimol (0.1μg/mouse) or ACPA (2ng/mouse) dose-dependently inhibited muscimol- and ACPA-induced SDL, respectively. Pre-test intra-CA1 administration of bicuculline (0.0625, 0.125 and 0.25μg/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. •ACPA 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.