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The effect of chronic amphetamine treatment on cocaine-induced facilitation of intracranial self-stimulation in rats

Psychopharmacology volume 231, pages 2461–2470 (2014)Cite this article

Abstract

Rationale

Chronic amphetamine treatment reduces cocaine self-administration in pre-clinical and clinical settings, and amphetamine has been proposed as a candidate medication for treatment of cocaine abuse.

Objective

The objective of the present study was to investigate whether chronic amphetamine treatment can decrease abuse-related cocaine effects in an assay of intracranial self-stimulation (ICSS).

Methods

Thirteen adult male Sprague-Dawley rats were equipped with intracranial electrodes targeting the medial forebrain bundle and trained to lever press for pulses of brain stimulation in a “frequency-rate” ICSS procedure. Cocaine (10 mg/kg) was administered before (day 0), during (days 7 and 14), and after (posttreatment days 1 and 3) 2 weeks of continuous treatment with either amphetamine (0.32 mg/kg/h, n = 7) or saline (n = 6) via osmotic pump.

Results

Prior to treatment, cocaine facilitated ICSS in all rats. Saline treatment had no effect on baseline ICSS or cocaine-induced facilitation of ICSS at any time. Conversely, amphetamine produced a sustained though submaximal facilitation of baseline ICSS, and cocaine produced little additional facilitation of ICSS during amphetamine treatment. Termination of amphetamine treatment produced a depression of baseline ICSS and recovery of cocaine-induced facilitation of ICSS.

Conclusions

These data suggest that chronic amphetamine treatment blunts expression of abuse-related cocaine effects on ICSS in rats.

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Abbreviations

ICSS:

Intracranial self-stimulation

MCR:

Maximum control rate

S.C.:

Subcutaneous

I.P.:

Intraperitoneal

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Acknowledgments

These studies were supported by National Institutes of Health grants F30-DA034478 (CTB) and R01-DA026946 (SSN).

Conflict of interest

There are no other conflicts of interest.

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Affiliations

  1. Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 N. 12th St., PO Box 980613, Richmond, VA, 23298, USA

    Clayton T. Bauer, Matthew L. Banks & S. Stevens Negus

Authors
  1. Clayton T. Bauer
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  2. Matthew L. Banks
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  3. S. Stevens Negus
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Correspondence to S. Stevens Negus.

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Bauer, C.T., Banks, M.L. & Negus, S.S. The effect of chronic amphetamine treatment on cocaine-induced facilitation of intracranial self-stimulation in rats. Psychopharmacology 231, 2461–2470 (2014). https://doi.org/10.1007/s00213-013-3405-1

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  • DOI: https://doi.org/10.1007/s00213-013-3405-1

Keywords

  • ICSS
  • Amphetamine
  • Cocaine
  • Withdrawal
  • Tolerance