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Discrete-trials heroin self-administration produces sensitization to the reinforcing effects of cocaine in rats

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Abstract

Rationale

The prevalence of cocaine use in opioid-dependent individuals is reportedly high, and the associated negative health and social consequences are severe and well documented. Sensitization of the reinforcing effects of cocaine has been demonstrated following noncontingent opioid exposure in animals; however, no preclinical studies have investigated the impact of opioid self-administration on cocaine’s reinforcing effects.

Objective

Experiments were designed to investigate whether access to heroin self-administration altered the subsequent reinforcing effects of cocaine.

Methods

Baseline responding for cocaine under a progressive ratio schedule was first established. Heroin was then self-administered under a 24-h discrete-trials procedure (DT5; access to heroin five times per hour). Subsequently, cocaine-maintained responding was reassessed.

Results

Here we demonstrate that 10 days of DT5 heroin self-administration (50 μg/kg per infusion) resulted in an increase in cocaine’s reinforcing effects at several doses across the cocaine dose–effect curve (0.38–3.0 mg/kg per infusion). These increases were relatively long lasting, exceeding the time course of a mild withdrawal syndrome.

Conclusions

The DT5×10-day history of heroin self-administration resulted in an upward shift in the cocaine dose–effect curve, suggesting that DT5 heroin self-administration produced an increase in potency and sensitization of the maximal effectiveness with which cocaine functions as a reinforcer. The present experiments contribute to a growing amount of preclinical evidence suggesting an impact of opioid exposure on the reinforcing effects of cocaine, which may partially explain the high incidence of cocaine use in opioid-dependent individuals.

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Acknowledgement

This research was supported by the National Institute on Drug Abuse (RO1DA12498).

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Authors and Affiliations

  1. Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-3270, USA

    Sara J. Ward

  2. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    Christopher Läck, Drake Morgan & David C. S. Roberts

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  1. Sara J. Ward
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  2. Christopher Läck
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  3. Drake Morgan
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  4. David C. S. Roberts
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Correspondence to Sara J. Ward.

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Ward, S.J., Läck, C., Morgan, D. et al. Discrete-trials heroin self-administration produces sensitization to the reinforcing effects of cocaine in rats. Psychopharmacology 185, 150–159 (2006). https://doi.org/10.1007/s00213-005-0288-9

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  • DOI: https://doi.org/10.1007/s00213-005-0288-9

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