Sex difference in the modulation of responding to an alcohol-predictive cue by an alcohol-associated context

BackgroundIn male rats, physical contexts that are associated with alcohol can invigorate responding to a discrete, alcohol-predictive conditioned stimulus (CS), and amplify priming-induced reinstatement. Here, we examined these effects as a function of biological sex. MethodsMale and female Long-Evans rats were acclimated to drinking ethanol (EtOH, 15% v/v) in their home cages. Next, they were trained to associate an auditory CS (10 s; white noise; 15 trials per session) with EtOH delivery (0.2 ml per CS; 3.0 ml per session) into a fluid port for oral intake. Training occurred in a distinctive context containing specific visual, olfactory, and tactile stimuli. During alternating sessions rats were exposed to a second context where they did not receive EtOH. At test, CS presentations occurred in both contexts without EtOH delivery. Rats then underwent extinction using repeated unreinforced presentations of the CS in both contexts. An alcohol-primed reinstatement test was then conducted, in which 0.2 ml of EtOH was presented both at the start of the session and during the first CS presentation, after which no EtOH was delivered for the remainder of the session. ResultsAt both test and reinstatement, male rats made significantly more CS port-entries in the context associated with alcohol delivery than in the context in which alcohol was never experienced. Unlike males, female rats made a similar number of CS port-entries at test in both the alcohol context and the neutral context. The reinstatement observed in female rats was not affected by context. ConclusionsThese findings identify novel sex differences in the capacity of an alcohol-associated context to modulate responding to a discrete, alcohol-predictive cue.