Brain-region Specificmodulation of Ethanol-induced Depression Ofgabaergic Neurons in the Reward Systemby the Nicotine Receptor Antagonistmecamylamine

Background. The nucleus accumbens (nAc) and the VTA are primary components of the mesolimbic dopamine system, which is activated by all drugs of abuse, including ethanol. GABAergic neurotransmission has repeatedly been shown to regulate the activity of dopaminergic neurons in the VTA, and the aim with this study was to define the involvement of nicotinic acetylcholine receptors (nAChRs) in mediating acute ethanol effects on GABAergic activity in the nAc and VTA of awake and freely moving mice. Methods. Multielectrode in vivo electrophysiology was performed in the VTA and nAc of awake and freely moving C57BL6/J mice receiving intraperitoneal injections of saline, ethanol (2.0 g/kg), and the non-competitive nAChR antagonist mecamylamine (1.0 mg/kg). Results. GABAergic firing rate and burst activity was significantly depressed following administration of ethanol as compared to saline in both the VTA and in the nAc. Pre-treatment with mecamylamine inhibited the ethanol-induced decrease in GABAergic firing rate in the VTA, while the reduced firing rate sustained following ethanol-administration in accumbal medium spiny projection neurons. The ethanol-induced decrease in VTA burst activity was not inhibited by mecamylamine. Conclusion. The data presented here shows that ethanol depresses GABAergic activity in the VTA and nAc of mice, and that nAChRs contribute to this modulation in the VTA. This finding is in line with previous studies of ethanol-induced dopamine-release, and supports an involvement of GABAergic neurons in regulating the activation of the mesolimbic dopamine-system by ethanol.