
Conditioned responding to drug-predictive discrete cues can be strongly modulated by drug-associated contexts.
We tested the hypothesis that differential recruitment of the nucleus accumbens (NAc) core and shell mediates responding to drug cues in a drug
vs non-drug context.
Rats were trained to discriminate between two 10-s auditory stimuli: one stimulus (CS
+) was paired with ethanol (10
% v
/v; 0.2
ml; oral) whereas the other (CS−) was not. Training occurred in operant conditioning chambers distinguished by contextual stimuli, and resulted in increased entries into the ethanol delivery port during the CS
+ when compared with the CS−. In experiment 1, port entries were then extinguished in a second context by withholding ethanol, after which context-induced renewal of ethanol-seeking was tested by presenting both stimuli without ethanol in the previous training context. This manipulation stimulated strong responding to the CS
+ in rats pretreated with saline in the core (
n=9) or shell (
n=10), which was attenuated by pharmacologically inactivating (muscimol
/baclofen; 0.1
/1.0
mM; 0.3
μl
/side) either subregion pretest. In experiment 2, after discrimination, training rats were habituated to a different context in which ethanol and both stimuli were withheld. Cue-induced ethanol-seeking was then elicited by presenting the CS
+ and CS− without ethanol in the different context. Saline-pretreated rats responded more to the CS
+ than the CS− (core
n=8; shell
n=9), and inactivating the core but not shell attenuated this effect.
These data highlight an important role for the core in cue-induced ethanol-seeking, and suggest that the shell is required to mediate the influence of contexts on conditioned ethanol-seeking.
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