Reinstatement of alcohol-seeking behavior by drug-associated discriminative stimuli after prolonged extinction in the rat

Clinical observations suggest that stimuli associated with the availability or consumption of ethanol can evoke subjective feelings of craving and tri gger episodes of relapse in abstinent alcoholics. To study the motivational significance of alcohol-related environmental cues experimentally, the eff ects of discriminative stimuli previously predictive of alcohol availabilit y on the reinstatement of ethanol-seeking behavior were examined. Wister ra ts were trained to lever-press for 10% (w/v) ethanol or water in the presen ce of distinct auditory cues. The rats were then subjected to an extinction phase where lever presses had no scheduled consequences. After extinction, the animals were exposed to the respective auditory cues without the avail ability of ethanol or water. Neither the ethanol (S-A(+)) nor water-associa ted (S-A(-)) auditory cue increased responding over extinction levels. In c ontrast, subsequent presentation of an olfactory cue associated with ethano l (S-O(+)), but not a water-associated (S-O(-)) cue significantly reinstate d lever pressing behavior in the absence of the primary reinforcer. Moreove r, responding elicited by the concurrent presentation of the S-O(+) and S-A (+) was selectively attenuated by the opiate antagonist naltrexone (0.25 mg /kg; sc). The results suggest that ethanol-associated cues can reinstate ex tinguished ethanol-seeking behavior in mts, but that the efficacy of these stimuli may be modality-specific. In addition, the present procedures may b e useful for studying neurobiological mechanisms of alcohol-seeking behavio r and relapse. (C) 1999 American College of Neuropsychopharmacology. Publis hed by Elsevier Science Inc.