Involvement of dorsal hippocampal and medial septal nicotinic receptors in cross state-dependent memory between WIN55, 212-2 and nicotine or ethanol in mice.

The present study examined whether nicotinic acetylcholine receptors (nAChRs) of the CA1 regions of the dorsal hippocampus and medial septum (MS) are involved in cross state-dependent memory retrieval between WIN55, 212-2 (WIN, a non-selective CB1/CB2 receptor agonist) and nicotine or ethanol. Memory retrieval was measured in one-trial step-down type passive avoidance apparatus in male adult mice. Pre-training intraperitoneal administration of WIN (0.1-1mg/kg) dose-dependently impaired memory retrieval when it was tested 24h later. Pre-test systemic administration of nicotine (0.6 and 0.7mg/kg, s.c.) or ethanol (0.5g/kg, i.p.) improved WIN-induced memory impairment, suggesting a cross state-dependent memory retrieval between the drugs. Pre-test intra-CA1 microinjection of nicotine (1 and 2μg/mouse) before systemic administration of an ineffective dose of nicotine (0.5mg/kg, s.c.) or ethanol (0.25g/kg) significantly reversed WIN-induced memory impairment. Pre-test intra-CA1 microinjection of mecamylamine (1 and 3μg/mouse) inhibited cross state-dependent memory between WIN and nicotine or ethanol. Moreover, pre-test intra-MS microinjection of nicotine (1 and 2μg/mouse) in combination with systemic administration of a lower dose of nicotine (0.5mg/kg), but not ethanol (0.25g/kg), improved memory impairment induced by pre-training administration of WIN. On the other hand, in the animals that received pre-training WIN and pre-test systemic administration of nicotine (0.7mg/kg), but not ethanol (0.5g/kg), pre-test intra-MS microinjection of mecamylamine (1-5μg/mouse) inhibited WIN-nicotine state-dependent memory retrieval. It should be noted that pre-test intra-CA1 or intra-MS microinjection of nicotine or mecamylamine by itself had no effect on memory retrieval and also could not reverse memory impairment induced by pre-training administration of WIN. It can be concluded that WIN and nicotine or WIN and ethanol can induce state-dependent memory retrieval. In addition, our results showed that a cross-state dependency between these drugs may be mediated through a cholinergic nicotinic mechanism.