¹Department of Behavioral Neuroscience, Portland Alcohol Research Center, Oregon Health & Science University, Portland, OR, USA

Correspondence: Dr CM Gremel, Section on In Vivo Neural Function, Laboratory for Integrative Neuroscience, NIAAA/NIH 5625 Fishers Lane, Room TS-20, Rockville, MD 20852, USA. Tel: +1 301 443 4228; Fax: +1 301 480 0466; E-mail: gremelc@mail.nih.gov

Received 23 May 2008; Revised 6 September 2008; Accepted 8 September 2008; Published online 1 October 2008.

Abstract

Although progress has been made identifying neural mechanisms underlying ethanol's primary reinforcing effects, few studies have examined the mechanisms mediating ethanol-induced conditioned effects. A recent lesion study suggests that expression of ethanol-conditioned behaviors depends upon an intact amygdala and nucleus accumbens core. However, specific mechanisms within these nuclei are unknown. In the present experiments, we used site-specific microinfusions of dopamine and NMDA receptor antagonists to examine the roles of accumbens and amygdala in the expression of ethanol conditioned place preference (CPP) in mice. In experiments 1 and 2, a D1/D2/D3 receptor antagonist (flupenthixol) was infused into accumbens or amygdala before testing, whereas experiment 3 used pretest infusions of an NMDA antagonist (AP-5) to examine the role of intra-accumbens NMDA receptors. Dopamine antagonism of accumbens was without effect, but intra-amygdala infusions of flupenthixol blocked CPP expression. Moreover, this effect was dependent upon dopamine antagonism within the basolateral nucleus but not the central nucleus of the amygdala. Antagonism of NMDA receptors in accumbens also blocked CPP expression. The present findings suggest that expression of the ethanol-conditioned response depends upon amygdala dopamine and accumbens NMDA receptors. These are the first studies in any species to show a role for amygdala dopamine receptors and the first studies in mice to implicate accumbens NMDA receptors in ethanol-induced conditioned effects.