Received for publication February 4, 2008.
Revised March 26, 2008.
Accepted for publication March 26, 2008.

Nicotinic acetylcholine receptors in the anterior, but not posterior, VTA mediate ethanol induced elevation of accumbal dopamine levels

Abstract

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 appears to be conflicting findings depending on methodology (electrophysiology, microdialysis or intra-cranial 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 (nAChR) in order 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. In order to detect a possible influence on phasic dopamine release the dopamine transporter inhibitor nomifensine was included in the accumbal perfusate. Also 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-anteriorVTA-nAc neuronal circuitry involved in the dopamine activating effects of ethanol.

Key words: alcohol, dopamine, in vivo microdialysis, nicotinic acetylcholine receptor, nucleus accumbens, ventral tegmental area