Withdrawal periods following extended access cocaine self-administration do not alter drug intake during binge or resistance to punished cocaine self-administration relapse

Drug addiction is characterized as a chronic and relapsing disorder which persists despite long periods of abstinence from the drug. Changes in subjective craving for the drug have been reported to increase with long periods of abstinence, a phenomenon identified as incubation. Incubation is a time-dependent progressive increase in drug-seeking behavior elicited by cues previously associated with cocaine availability. While there have been many studies that have illustrated that length of withdrawal period is highly correlated to drug craving and seeking, this phenomenon does not seem to apply to traditional drug-induced relapse models. Here, we investigated the role of withdrawal periods on relapse to cocaine in "binge" and punishment models of cocaine self-administration. Rats were trained to self-administer cocaine in an extended access self administration paradigm (6 hour test sessions) for 10 days. After the final day of cocaine SA, rats were assigned to either a 1, 14 or 30 days of withdrawal period, following which rats were exposed to a 12-hour binge session where they were allowed unlimited access to cocaine. Drug addiction is further characterized by one's willingness to continue to take drugs despite negative consequences. We established a punishment model where following withdrawal (1 or 14 days) from cocaine self-administration, rats were then given a histamine/cocaine mixture for 6 hours.;Surprisingly, despite the imposed 14 and 30 day withdrawal periods, animals self-administered an equal amount of cocaine during the 12-hour binge as animals with a brief 1 day withdrawal period. Similar results were observed during the punishment relapse model. Animals exposed to a 14-day withdrawal took the same amount of drug as animals exposed to 1-day withdrawal despite that the drug intake had a negative consequence. Although these data do not support the incubation hypothesis, the findings demonstrate a great deal of stability of drug-taking behavior despite time of abstinence. We are preparing to examine the transcriptional mechanisms that mediate such behavioral stability in an attempt to identify novel molecular targets that may provide a therapeutic intervention.