Vendor differences in alcohol consumption and the contribution of dopamine receptors to Pavlovian-conditioned alcohol-seeking in Long-Evans rats

Abstract

Drug-associated environmental stimuli elicit craving in humans and drug-seeking in animals. We tested the hypothesis that Pavlovian-conditioned alcohol-seeking is mediated by dopamine, using rats from two vendors. Male, Long-Evans rats (220-240 g) from Charles River (St-Constant, QC, Canada) and Harlan Laboratories (Indianapolis, IN, USA) received 21 sessions of intermittent, 24-h access to ethanol (15 %, v/v) and water in the home-cage. Subsequently, rats were trained to discriminate between one conditioned stimulus (CS+) that was paired with ethanol (0.2 ml per CS+) and a second stimulus (CS-) that was not. Entries into a fluid port where ethanol was delivered were recorded. Next, rats were exposed to a different context where cues and ethanol were withheld. At test, responding to the CS+ and CS- without ethanol was assessed in the second, non-alcohol context. Injections (1 ml/kg; s.c.) of the dopamine D1-receptor antagonist SCH 23390 (0, 3.33, and 10 μg/kg) or dopamine D2-receptor antagonist eticlopride (0, 5, and 10 μg/kg) were administered before test. Home-cage alcohol consumption was higher in Harlan rats than Charles River rats. At test, saline-treated rats responded more to the alcohol-predictive CS+ than the CS-. While SCH 23390 attenuated CS+ responding in rats from both vendors, eticlopride reduced CS+ responding in Harlan rats only. Subsequently, SCH 23390 but not eticlopride attenuated CS+ responding when the CS+ was again paired with ethanol. These results indicate important differences in alcohol consumption in Long-Evans rats from different suppliers, and highlight a novel role for dopamine in Pavlovian-conditioned alcohol-seeking.