Abstract

Physical contexts that are associated with alcohol can amplify responding to discrete, alcohol-predictive cues in males. Here, we examined the contextual modulation of responding to discrete alcohol-predictive cues as a function of biological sex and the role of dopamine neurotransmission at D2-like receptors. Male and female rats that have previously consumed alcohol (15%; v/v) were trained to associate an auditory CS (10 s; 15 trials per session) with alcohol delivery (0.2 ml/ CS), in a distinctive multi-modal context (alcohol context). During alternating sessions rats were exposed to a second context where they did not receive alcohol (neutral context). In Experiment 1, CS presentations occurred in both contexts without alcohol delivery at test. Rats then underwent extinction using repeated unreinforced presentations of the CS in both contexts. Next, an alcohol-primed reinstatement test was conducted, in which 0.2 ml of alcohol was presented both at the start of the session and during the first CS presentation, after which no alcohol was delivered. At both tests, CS-elicited responding was amplified in the alcohol-associated context compared to the neutral context in males. CS-elicited responding was similar in the alcohol-associated context and the neutral context in female rats. In Experiment 2, rats received administration (s.c.) of D2-like receptor antagonist eticlopride (10 μg/kg) 15 min prior to test. Eticlopride significantly attenuated CS-elicited responding in both sexes and contexts. These findings identify novel sex differences in the capacity of an alcohol-associated context to modulate responding to a discrete alcohol-predictive cue and suggests that dopamine neurotransmission at D2-like receptors is critical for cue-elicited responding.

Keywords: Alcohol, Sex Differences, Context, Cue, Pavlovian Conditioning, Dopamine, Eticlopride, D2-like Receptors