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.
Hodge
C W
CW
Department of Physiology and Pharmacology, Wake Forest University, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
Samson
H H
HH
Chappelle
A M
AM
D000428:Alcohol Drinking / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001931:Brain Mapping; D008032:Limbic System / Q000503:physiopathology; D008297:Male; D008636:Mesencephalon / Q000503:physiopathology; D009042:Motivation; D009434:Neural Pathways / Q000503:physiopathology; D009714:Nucleus Accumbens / Q000503:physiopathology*; D051381:Rats; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D012646:Self Administration
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2