Separable roles of the nucleus accumbens core and shell in context- and cue-induced alcohol-seeking.
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 microl/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.
Chaudhri
Nadia
N
Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA 94608,USA. nchaudhri@gallo.ucsf.edu
Sahuque
Lacey L
LL
Schairer
William W
WW
Janak
Patricia H
PH
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D016739:Behavior, Addictive; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003463:Cues; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans
D000431:Ethanol