Hippocampal nicotinic receptors have a modulatory role for ethanol and MDMA interaction in memory retrieval

The aim of the current study was to examine the effect of dorsal hippocampal nicotinic acetylcholine receptors (nAChRs) activation on the functional interaction between ethanol and 3,4-methylenedioxyN-methylamphetamine (MDMA or ecstasy) in memory retrieval. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated and memory retrieval was measured in a stepdown type passive avoidance apparatus. Post-training or pre-test systemic administration of ethanol (1 g/kg, i.p.) induced amnesia. Pre-test administration of ethanol reversed pre-training ethanol-induced amnesia, suggesting ethanol state-dependent learning. Pre-test intra-CA1 microinjection of different doses of MDMA (0.25-1 mu g/mouse) with an ineffective dose of ethanol (0.25 g/kg, i.p.) also induced amnesia. Interestingly, pre-test intra-CAI microinjection of MDMA (0.25-1 mu g/mouse) potentiated ethanol state-dependent learning. On the other hand, the activation of the dorsal hippocampal nAChRs by pretest microinjection of nicotine (0.1-1 mu g/mouse, intra-CA1) improved amnesia induced by the co administration of MDMD and ethanol. It is important to note that intra-CA1 microinjection of the same doses of MDMA or nicotine could not affect memory formation by itself. Pre-test intra-CA1 microinjection of nicotine (0.3-0.9 mu g/mouse) could not reverse amnesia induced by pre-training administration of ethanol while this treatment enhanced MDMA response on ethanol state-dependent learning. Thus, it can be concluded that there may be functional interactions among ethanol, MDMA and nicotine via the dorsal hippocampal nicotinic acetylcholine receptor mechanism in memory retrieval and drug state dependent learning. (C) 2017 Elsevier B.V. All rights reserved.