Effects of abstinence or extinction on cocaine seeking as a function of withdrawal duration.

The resumption of drug-seeking behavior after abstinence or extinction is commonly studied model for relapse in addiction. For the benefits of extinction training over a given withdrawal period to be determined, it is necessary to discriminate between the potentially overlapping occurrence of incubation with that of spontaneous recovery. This comparison has been assessed using a between-subjects design in groups of abstinent and extinguished rats tested at various withdrawal periods after cocaine self-administration. Multiple forms of priming were used to evoke the resumption of drug seeking, as different priming stimuli have been reported to use distinct neurobiological mechanisms and therefore may exhibit different temporal characteristics. In abstinent animals (30 days), neither the noncontingent conditioned stimuli-primed nor the noncontingent cocaine-primed drug seeking displayed incubation, whereas the drug seeking provoked by exposure to the contextual cues of the operant chamber significantly increased. In extinguished animals, evidence of spontaneous recovery of responding was observed after priming with exposure to either contextual or cocaine-priming stimuli. Finally, extinction training remained effective in reducing the reinstatement response levels after contextual or cocaine priming even if such training was initiated after an extended period (24 days) of abstinence. These findings provide further insight into the time-dependent effects of abstinence and extinction on the resumption of drug-seeking behavior.