Context-induced relapse of conditioned behavioral responding to ethanol cues in rats

Background: The environmental context in which drug-conditioned cues are encountered could modulate the capacity of such cues to trigger relapse in abstinent addicts. We explored this hypothesis using a behavioral animal model. Methods: Rats were trained to discriminate between two auditory stimuli; the first (CS+) was paired with 10% ethanol and the second (CS-) was presented without ethanol. Training occurred in operant conditioning chambers equipped with distinct contextual stimuli, and entries into the ethanol delivery port during the stimuli were measured. Behavior was then extinguished by presenting both stimuli without ethanol in a second, different context. Context-dependent renewal of port entries was tested by presenting the CS+ and CS- without ethanol in the original training context. Results: At test, port entries during the CS+ increased compared with extinction levels, while responding during the CS- remained unchanged (n = 11). This effect was attenuated after multiple extinction sessions in three distinct contexts (n = 18), compared with an equivalent number of extinction sessions in a single unique context (n = 16). Context-dependent renewal of port entries was also observed to a CS+ paired with 14% sucrose (n = 7) but not to a CS+ paired with 2% sucrose (n = 8). Conclusions: Environmental contexts can trigger the relapse of behavioral responding to ethanol- and sucrose-predictive cues in rats. For ethanol, this effect can be reduced by extinguishing responses to the ethanol cue in multiple distinct contexts, a manipulation that could increase the efficacy of cue-reactivity treatments for addiction.