Coregulation of ethanol discrimination by the nucleus accumbens and amygdala.
BACKGROUND
Activation of GABA(A) receptors in the amygdala or nucleus accumbens produces discriminative stimulus effects that substitute fully for those of systemically administered ethanol. This study was conducted to determine if GABA(A) receptors in the amygdala and nucleus accumbens interactively modulate ethanol discrimination.


METHODS
Male Long-Evans rats were trained to discriminate between intraperitoneal injections of ethanol (1 g/kg) and saline on a 2-lever drug discrimination task. The rats were then surgically implanted with bilateral injection cannulae aimed at the nucleus accumbens and the amygdala.


RESULTS
Infusion of the GABA(A) agonist muscimol in the nucleus accumbens resulted in full substitution for systemically administered ethanol. Concurrent infusion of the GABA(A) antagonist bicuculline in the amygdala shifted the muscimol substitution curve in the nucleus accumbens 10-fold to the right.


CONCLUSIONS
These results indicate that blockade of GABA(A) receptors in the amygdala significantly reduces the potency of the GABA(A) agonist in the nucleus accumbens. This suggests that the ethanol-like stimulus effects of GABA(A) receptor activation in the nucleus accumbens are modulated by GABA(A) receptor activity in the amygdala. These data support the hypothesis that the addictive stimulus properties of alcohol are mediated by GABAergic transmission in a neural circuit involving the amygdala and nucleus accumbens.
Besheer
Joyce
J
Bowles Center for Alcohol Studies, Thurston-Bowles Building; CB#7178, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Cox
Amy A
AA
Hodge
Clyde W
CW
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D000431:Ethanol