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Heroin self-administration and reinstatement of heroin-seeking in adolescent vs. adult male rats

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Abstract

Rationale

Heroin abuse is prevalent among teenagers, and early onset drug use might predict long-term drug dependence. However, adolescent sensitivity to drug reinforcement has not been explored thoroughly in animal models.

Objectives

This study aimed to compare intravenous (i.v.) self-administration of heroin, as well as extinction and reinstatement of heroin-seeking, in adolescent vs. adult male rats.

Methods

Adolescent (35 days old at start) and adult (86 days old at start) male Sprague–Dawley rats spontaneously acquired lever pressing maintained by i.v. heroin infusions. In experiment 1, self-administration was tested on a fixed ratio 1 schedule of reinforcement (0.05 and 0.025 mg/kg per infusion), followed by within-session extinction and reinstatement tests after 1 or 12 days of abstinence. In experiment 2, self-administration was tested on a progressive ratio schedule (0.0125–0.1 mg/kg per infusion), followed 12 days later by a single test of extinction responding in the presence of cues.

Results

In experiment 1, adolescent rats self-administered more heroin than adults. After 1 or 12 days of abstinence, adolescents exhibited less heroin-seeking than adults, although levels of heroin-seeking increased over abstinence period for both age groups. In experiment 2, adolescents and adults reached the same maximal response ratio (breakpoint), although adolescents earned more infusions when response requirements were low. For extinction responding in the presence of cues, heroin-seeking was similar across ages.

Conclusions

Lower levels of heroin-seeking suggest that younger rats are less sensitive than adults to some residual effects of heroin intake.

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Acknowledgments

The authors would like to thank Chen Li, Bonnie Williams, Patrick Dunigan, and Adria Lee for their excellent technical assistance, as well as Dr. D.C.S. Roberts for helpful comments on the data. This research was supported in part by a National Institute on Drug Abuse B/START grant to KJF (1 RO3 DA020110-01), the Center for Behavioral Neuroscience NSF Science & Technology Center (IBN-9876754), and a seed grant from the Brains & Behavior program at Georgia State University. These experiments complied with the current laws of the USA.

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

    James M. Doherty & Kyle J. Frantz

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  1. James M. Doherty
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  2. Kyle J. Frantz
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Correspondence to Kyle J. Frantz.

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Doherty, J.M., Frantz, K.J. Heroin self-administration and reinstatement of heroin-seeking in adolescent vs. adult male rats. Psychopharmacology 219, 763–773 (2012). https://doi.org/10.1007/s00213-011-2398-x

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