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NEUROPHARMACOLOGY

Nicotinic Acetylcholine Receptors in the Anterior, but Not Posterior, Ventral Tegmental Area Mediate Ethanol-Induced Elevation of Accumbal Dopamine Levels

Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (M.E., E.L., R.S., P.C., B.S.); and Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden (B.S.)

Ethanol-induced elevations of accumbal dopamine levels have been linked to the reinforcing properties of the drug. However, it has not yet been demonstrated where the primary point of action of ethanol is in the mesolimbic dopamine system, and there appear to be conflicting findings depending on methodology (electrophysiology, microdialysis, or intracranial self-administration). We have suggested that ethanol acts in the nucleus accumbens (nAc), where it activates a neuronal loop involving ventral tegmental nicotinic acetylcholine receptors (nAChRs) to elevate dopamine levels in the nAc. Application of ethanol in the nAc results in elevated dopamine levels in the same brain region, whereas administration in the anterior ventral tegmental area (VTA) fails to influence dopamine output. In the present study, we were able to repeat these findings. In addition, application of ethanol in the posterior VTA also failed to influence nAc dopamine levels. Perfusion of the nAChR antagonist mecamylamine in the anterior VTA completely blocked the elevation of accumbal dopamine levels observed after ethanol perfusion in nAc, whereas mecamylamine in the posterior VTA had no effect. To detect a possible influence on phasic dopamine release, the dopamine transporter inhibitor nomifensine was included in the accumbal perfusate. In addition, under these conditions, ethanol in the anterior or posterior VTA failed to influence dopamine release in the nAc. These results support previous suggestions of distinct functions of the anterior and posterior VTA and give further evidence for our hypothesis of a nAc-anterior VTA-nAc neuronal circuitry involved in the dopamine-activating effects of ethanol.

Address correspondence to: Mia Ericson, Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, P.O. Box 410, 405 30 Göteborg, Sweden. E-mail: mia.ericson{at}neuro.gu.se