RATIONALE: Abstinence from drug occurs in human addicts for several reasons, including the avoidance of adverse consequences. OBJECTIVES: To explore a model of drug use in the face of adverse consequences in rats through intermittent punishment of drug seeking and to investigate whether the ability to withhold seeking responses depends upon the duration of drug history. MATERIALS AND METHODS: Rats were trained under a seeking-taking chained schedule with sucrose or cocaine as reinforcer. Pressing the seeking lever gave access to the taking lever, and a single press on this lever delivered the reinforcer after which the seeking-taking chain recycled. During punishment, half of the seeking links terminated with a mild foot shock without access to the taking link. RESULTS: After a moderate history of reinforcement, punishment of the terminal response in the seeking link suppressed both sucrose- and cocaine-seeking responses. By contrast, rats with an extended cocaine history were more resistant to punishment than those with a moderate cocaine history. This enhanced resistance to punishment was due to a sub-group of rats that showed minimal or no suppression of drug seeking. No differences in suppression of sucrose seeking were observed in animals with moderate versus extended sucrose histories. CONCLUSIONS: These results suggest that an extended drug self-administration history decreases the ability of vulnerable rats to suppress their drug seeking.
RATIONALE: Abstinence from drug occurs in human addicts for several reasons, including the avoidance of adverse consequences. OBJECTIVES: To explore a model of drug use in the face of adverse consequences in rats through intermittent punishment of drug seeking and to investigate whether the ability to withhold seeking responses depends upon the duration of drug history. MATERIALS AND METHODS: Rats were trained under a seeking-taking chained schedule with sucrose or cocaine as reinforcer. Pressing the seeking lever gave access to the taking lever, and a single press on this lever delivered the reinforcer after which the seeking-taking chain recycled. During punishment, half of the seeking links terminated with a mild foot shock without access to the taking link. RESULTS: After a moderate history of reinforcement, punishment of the terminal response in the seeking link suppressed both sucrose- and cocaine-seeking responses. By contrast, rats with an extended cocaine history were more resistant to punishment than those with a moderate cocaine history. This enhanced resistance to punishment was due to a sub-group of rats that showed minimal or no suppression of drug seeking. No differences in suppression of sucrose seeking were observed in animals with moderate versus extended sucrose histories. CONCLUSIONS: These results suggest that an extended drug self-administration history decreases the ability of vulnerable rats to suppress their drug seeking.
Authors: Irina N Krasnova; Nathan J Marchant; Bruce Ladenheim; Michael T McCoy; Leigh V Panlilio; Jennifer M Bossert; Yavin Shaham; Jean L Cadet Journal: Neuropsychopharmacology Date: 2014-03-03 Impact factor: 7.853