Long-lasting resistance to extinction of response reinstatement induced byethanol-related stimuli: Role of genetic ethanol preference

Background: The conditioning of ethanol's reinforcing effects with specific environmental stimuli is thought to be a critical factor in long-lasting r elapse risk associated with alcoholism. To study the significance of such l earning factors in the addictive potential of ethanol, this experiment was designed (1) to characterize the effects of stimuli associated with alcohol availability on the reinstatement of responding at a previously ethanol-pa ired lever in rats with genetically determined ethanol preference versus no npreference and (2) to examine the persistence of the motivating effects of these stimuli over time. Methods: Mate alcohol-preferring (P) and alcohol-nonpreferring (NP) rats we re trained to operantly self-administer ethanol (10% w/v) or water on a fix ed-ratio 1 schedule in a 30-min daily session. Ethanol and water sessions w ere scheduled in random sequence across training days. Ethanol availability was signaled by an olfactory discriminative stimulus (banana extract, S'), and each lever press was paired with brief presentation of the conditionin g chamber's house light (CS'). The discriminative stimulus signaling water availability (i.e., nonreward) consisted of anise odor (S-), and lever-resp onses during water sessions were paired with a brief white noise generation (CS-). The rats then were placed on extinction conditions during which eth anol and water, as well as the corresponding stimuli, were withheld. The ef fects of noncontingent exposure to the S' versus S- paired with response-co ntingent presentation of the CS' versus CS- on responding at the previously active lever were then determined in 30-min reinstatement sessions. To stu dy the resistance to extinction of the effects of the ethanol-associated st imuli, additional tests were conducted at 3-day intervals for a total of 50 days. Results: The number of ethanol-reinforced responses during self-administrat ion training was significantly greater in P than in NTP rats (p<0.01). Afte r extinction, a significant recovery of responding was observed in both gro ups of rats under the stimulus conditions associated: with ethanol (S+/CS+) but not those associated with water (S-/CS-). However, the response reinst atement was significantly greater in P than NP rats (p<0.01). In addition, the results revealed a considerable resistance to extinction to the effects of the ethanol-associated stimuli. Throughout the 50-day test period, resp onding remained significantly above extinction levels in both P and NP rats (p<0.01), but with an overall greater number of responses in P than NP rat s (p<0.05). Conclusions: The results support the hypothesis that conditioning factors c ontribute importantly to compulsive ethanol seeking and long-lasting vulner ability to relapse. In addition, the results suggest that genetic predispos ition toward heightened ethanol intake extends to greater susceptibility to the motivating effects of ethanol-related environmental stimuli.