The role of context on responding to an alcohol-predictive cue in female and male rats

In male rats, physical contexts that are associated with alcohol can amplify the response to a discrete, alcohol-predictive conditioned stimulus (CS), and amplify prime-induced reinstatement. Here, we examined these effects as a function of biological sex. Male and female Long-Evans rats were acclimated to drinking ethanol (15% v/v) in their home cages. Next, they were trained to associate an auditory conditioned stimulus (CS) (10 s; white noise or clicker; 15 trials per session) with ethanol 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 wherein they did not receive ethanol. At test, CS trials occurred in both contexts without ethanol 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 ethanol was presented at the start of the session and during the first CS trial, after which no ethanol was delivered for the remainder of the session. At 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 the test in both the alcohol context and the neutral context. The reinstatement observed in female rats was also not affected by context. These findings suggest that the capacity of an alcohol-associated context to modulate responding to a discrete, alcohol-predictive cue is less pronounced in female than male rats.