Alcohol Self‐Administration: Further Examination of the Role of Dopamine Receptors in the Nucleus Accumbens

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Abstract
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 μ/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 μg) produced no effect on ethanol self‐administration. The D1‐like antagonist SCH 23390 (0.5 to 2.0 μg) 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 μg) increased total responses and response rate, whereas higher doses (4.0 to 10.0 μg) decreased total responding as a result of early termination. The D2‐like antagonist raclopride (0.1 to 1.0 μg) 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.