Alcohol Self-administration: Further Examination of the Role of Dopamine Receptors in the Nucleus Accumbens

One of the functions of the mesolimbic dopamine (DA) system is to regulate the process of reinforcement, a process that is thought to influence drug self-administration. This study tested the effects of centrally administered DA receptor ligands on ethanol self-administration behavior. Long-Evans rats were trained to lever press on a fixed-ratio 4 schedule of ethanol (10% v/v) reinforcement. DA agonists and antagonists were then bilaterally microinjected (0.5 microliter/side) into the nucleus accumbens (N Acc) 10-min before sessions to test for effects on the onset, maintenance, and termination of ethanol self-administration. Infusions of the D1-like agonist SKF 38393 (0.03 to 3.0 micrograms) produced no effect on ethanol self-administration. The D1-like antagonist SCH 23390 (0.5 to 2.0 micrograms) reduced total responding by decreasing the time course of self-administration without altering response rate. The D2-like agonist quinpirole produced a biphasic effect on self-administration. Quinpirole (1.0 microgram) increased total responses and response rate, whereas higher doses (4.0 to 10.0 micrograms) decreased total responding as a result of early termination. The D2-like antagonist raclopride (0.1 to 1.0 microgram) reduced total responding by decreasing time course and response rate. Co-administration of either SKF 38393 or SCH 23390 with quinpirole prevented the behavioral effects observed with the low doses of quinpirole. Thus, in the N Acc either increased activation of D1-like receptors or their blockade can affect the expression of the behavioral effects of the D2-like agonist. This suggests that some intermediate level of D1 activation is required to observe the D2 effect. The decreases in total responding produced by raclopride were enhanced by co-administration of SKF 38393, but not altered by SCH 23390, thus suggesting that D1-like and D2-like receptors in the N Acc interact in the regulation of ethanol self-administration in a manner similar to their interactive regulation of other behaviors.