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Attenuated incubation of cocaine seeking in male rats trained to self-administer cocaine during periadolescence

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Abstract

Rationale and objectives

Although onset of drug use during adolescence appears to increase long-term vulnerability to drug dependence in humans, relatively little is known about extinction and reinstatement of drug seeking after periadolescent onset of drug self-administration in laboratory animals. Furthermore, although cue-induced reinstatement of cocaine seeking increases progressively during abstinence from cocaine self-administration in adult subjects, this “incubation of cocaine craving” remains unexplored after adolescent drug intake in animal models.

Materials and methods

We allowed periadolescent (postnatal day (PND) 35 at start) and adult (PND 83–95 at start) male Wistar rats to self-administer cocaine (0.36 mg/kg/infusion) in 2-h daily sessions on a fixed ratio 1 schedule of reinforcement over 14 days. Then, we compared extinction and cue-induced or cocaine priming-induced reinstatement (10 mg/kg cocaine, intraperitoneal) of cocaine seeking in both age groups after 30 days of abstinence in home cages. In separate cohorts, we tested for time-dependent increases in cue-induced reinstatement over approximately 1, 14, 30, or 60 days of abstinence in both age groups.

Results

Adolescent and adult rats self-administered similar amounts of cocaine. Subsequent cue-induced reinstatement was lower in the adolescent-onset group after a 30-day abstinence period, but cocaine priming-induced reinstatement did not differ across ages. Also, extinction responding and time-dependent increases in cue-induced reinstatement (incubation) were less pronounced in rats that took cocaine as adolescents compared with adults.

Conclusions

Surprisingly, these results may reflect resistance among adolescent subjects to some enduring effects of drug self-administration, such as reward learning.

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Acknowledgements

The authors would like to thank Bonnie Williams, James Doherty, Yvonne Ogbomnwan, and Sasha Nikolaevskaya for their excellent laboratory assistance, as well as Drs. G. Koob and Y. Shaham for comments on this manuscript. Our research was supported in part by the Center for Behavioral Neuroscience, an NSF Science and Technology Center, under agreement IBN-9876754.

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  1. Neuroscience Institute, Georgia State University, P.O. Box 5030, Atlanta, GA, 30302-5030, USA

    Chen Li & Kyle J. Frantz

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  1. Chen Li
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Correspondence to Kyle J. Frantz.

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Li, C., Frantz, K.J. Attenuated incubation of cocaine seeking in male rats trained to self-administer cocaine during periadolescence. Psychopharmacology 204, 725–733 (2009). https://doi.org/10.1007/s00213-009-1502-y

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