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Methamphetamine discrimination and in vivo microdialysis in squirrel monkeys

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Abstract

Rationale

Characterization of changes in dopamine activity associated with the discriminative-stimulus effects of methamphetamine (MA) and related stimulants will aid our understanding of the role of dopamine in mediating the subjective effects of this drug class.

Objectives

Squirrel monkeys were studied to explore the relationship between discriminative-stimulus effects of psychomotor stimulant drugs and their ability to increase extracellular dopamine levels in the caudate nucleus.

Methods

The ability of MA, cocaine and methylphenidate (0.01–0.32 mg/kg) to produce MA-like discriminative-stimulus effects was assessed in monkeys trained to discriminate IM injections of 0.32 mg/kg MA from saline. In addition, the effects of a range of MA doses (0.01–0.32 mg/kg) and selected doses of cocaine, methylphenidate and the GBR 12909 analog AM2517 on extracellular dopamine in the caudate nucleus were determined by microdialysis.

Results

MA, cocaine and methylphenidate produced dose-related increases in responding on the MA-associated lever and fully substituted at higher doses. In microdialysis studies, doses of MA, cocaine, methylphenidate, and AM2517 that produced 100% MA-lever responding produced comparable increases in caudate dopamine (to approximately 250% of control values). However, comparable increases in extracellular dopamine also were observed following a lower dose of MA (0.1 mg/kg) that produced, on average, 42% MA-lever responding. Moreover, increases in dopamine levels following administration of 0.03 and 0.1 mg/kg MA persisted after responding on the MA-associated lever had subsided.

Conclusions

Taken together, these results support a prominent role for dopamine in MA-like discriminative-stimulus effects, but are consistent with the additional involvement of other neurochemical actions.

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Acknowledgements

The authors gratefully acknowledge the technical assistance of Ms. Michelle Eaton and Ms. Anne Smith for technical assistance. This research was supported by National Institute on Drug Abuse (NIDA) grants DA03774, DA10566, DA07252, DA11949, DA07312 and DA00493.

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Author notes

  1. Paul W. Czoty

    Present address: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA

Authors and Affiliations

  1. McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA

    Paul W. Czoty & Jack Bergman

  2. Center for Drug Discovery and Departments of Pharmaceutical Sciences and Molecular Cell Biology, University of Connecticut Storrs, CT 06269, USA

    Alexandros Makriyannis

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  1. Paul W. Czoty
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Correspondence to Jack Bergman.

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Czoty, P.W., Makriyannis, A. & Bergman, J. Methamphetamine discrimination and in vivo microdialysis in squirrel monkeys. Psychopharmacology 175, 170–178 (2004). https://doi.org/10.1007/s00213-004-1798-6

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  • DOI: https://doi.org/10.1007/s00213-004-1798-6

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