Effects of raclopride in the nucleus accumbens on ethanol seeking and consumption.

Abstract

Nucleus accumbens dopamine has been shown to play a role in the processing of behaviorally relevant stimuli and to mediate ethanol-reinforced responding. Previous research that used a fixed-ratio schedule of responding maintained by the presentation of small dippers (0.1 ml) of ethanol demonstrated that the dopamine D2 antagonist, raclopride, decreased total responding for ethanol by both delaying the onset of responding and causing the early termination of lever-press behavior. Because these studies required animals to continuously respond to obtain access to small amounts of ethanol over a period of self-administration, this procedure assessed a combination of appetitive (seeking) and consummatory (drinking) behavior. The paradigm used in the present study separated the appetitive or seeking response from the consummatory response to assess the effects of raclopride on both types of ethanol-related behaviors. Male Long-Evans rats were trained to emit a fixed number of lever-press responses that resulted in access to a drinking tube that contained 10% ethanol for 20 min, once each day. We measured the effects of microinjections of raclopride (1.0, 3.0, and 10.0 microg/subject) into the nucleus accumbens, before the sessions, on appetitive and consummatory responding. Raclopride delayed the onset of ethanol-seeking (appetitive responding) at all doses and decreased the number of responses made at the low and high doses. The rate of responding, however, was unaffected. Raclopride had no effect on the latency to begin consuming ethanol or on any of the characteristics of the initial bout of ethanol intake at all doses tested. Total ethanol intake was decreased, after an initially "normal" pattern of self-administration, following only the highest dose of raclopride. Mean ethanol intake (g/kg) was 0.54 (+/-0.03) after no injection, 0.51 (+/-0.04) after sham treatment, and 0.38 (+/-0.05) after 10 microg of raclopride. The procedural separation of the seeking and intake responses used in this experiment allowed us to assess the effects of dopamine receptor antagonism in the nucleus accumbens on these two different behaviors. Overall, appetitive responding that preceded the delivery of an ethanol solution was more sensitive to raclopride treatment than was consummatory responding. These findings are consistent with a stimulus-processing function of the mesolimbic dopamine system.