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Cross-sensitization of the reinforcing effects of cocaine and amphetamine in rats

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Abstract

Rationale

Cross-sensitization between cocaine and amphetamine has been demonstrated in different behavioral paradigms. There is a relative paucity of studies examining whether cross-sensitization occurs between amphetamine and cocaine when both are self-administered.

Objective

The current study was designed to test whether animals sensitized to the reinforcing effects of cocaine would show cross-sensitization of the reinforcing effects of amphetamine, using a self-administration paradigm.

Materials and methods

Male, Sprague–Dawley rats were trained to self-administer cocaine and given limited or high exposure to cocaine under a fixed ratio (FR) 1 procedure. After the initial exposure to cocaine, animals self-administered cocaine (1.5 mg/kg per injection) under a progressive ratio (PR) procedure. Subsequently, breakpoints on a PR schedule and rates of intake on an FR schedule maintained by different doses of amphetamine were assessed.

Results

Animals with high initial exposure to cocaine (40 injections of 1.5 mg/kg per injection per day for 5 days) showed stable breakpoints throughout testing. Animals given limited initial cocaine exposure (20 injections of 0.75 mg/kg per injection for 1 day) produced a gradual increase in breakpoints maintained by cocaine over time (i.e., sensitization of the reinforcing effects of cocaine). When subsequently tested with amphetamine, the dose–effect curve was shifted upward in the limited-exposure group relative to the high-exposure group, suggesting cross-sensitization of the reinforcing effects of amphetamine.

Conclusions

Sensitization of the reinforcing effects of cocaine resulted in cross-sensitization of the reinforcing effects of amphetamine. This phenomenon occurs even when both drugs are self-administered.

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Acknowledgments

This study is supported by the National Institute of Drug Abuse grant R01DA14030 awarded to DCSR. DM was supported by NIH grant K01DA13957.

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Author notes

  1. Yu Liu

    Present address: National Institution on Drug Dependence, Peking University, 38 Xueyuan Road, Beijing, 10083, People’s Republic of China

  2. Drake Morgan

    Present address: Department of Psychiatry, Division of Addiction Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, USA

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC, 27157, USA

    Yu Liu, Drake Morgan & David C. S. Roberts

Authors
  1. Yu Liu
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  2. Drake Morgan
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  3. David C. S. Roberts
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Correspondence to David C. S. Roberts.

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Liu, Y., Morgan, D. & Roberts, D.C.S. Cross-sensitization of the reinforcing effects of cocaine and amphetamine in rats. Psychopharmacology 195, 369–375 (2007). https://doi.org/10.1007/s00213-007-0909-6

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  • DOI: https://doi.org/10.1007/s00213-007-0909-6

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