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Differential effects of amphetamine isomers on dopamine release in the rat striatum and nucleus accumbens core

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Abstract

Rationale

Current medications for attention-deficit/hyperactivity disorder (ADHD) include some single isomer compounds [dextroamphetamine (d-amphetamine, dexedrine) and dexmethylphenidate (Focalin)] and some racemic compounds [methylphenidate and mixed-salts amphetamine (Adderall)]. Adderall, which contains approximately 25% l-amphetamine, has been successfully marketed as a first-line medication for ADHD. Although different clinical effects have been observed for d-amphetamine, Adderall, and benzedrine; potential psychopharmacological differences on the level of neurotransmission between d-amphetamine and l-amphetamine have not been well characterized.

Objectives

To evaluate potential differences in the isomers, we used the technique of high-speed chronoamperometry with Nafion-coated single carbon-fiber microelectrodes to measure amphetamine-induced release of dopamine (DA) in the striatum and nucleus accumbens core of anesthetized male Fischer 344 rats. Amphetamine solutions were locally applied by pressure ejection using micropipettes.

Results

The presence of l-amphetamine in the d,l-amphetamine solutions did not cause increased release of DA but did change DA release kinetics. The d,l-amphetamine-evoked signals exhibited significantly faster rise times and shorter signal decay times. This difference was also observed in the nucleus accumbens core. When l-amphetamine was locally applied, DA release was not significantly different in amplitude, and it exhibited the same rapid kinetics of d,l-amphetamine.

Conclusions

These data support the hypothesis that amphetamine isomers have different effects on release of DA from nerve endings. It is possible that l-amphetamine may have unique actions on the DA transporter, which is required for the effects of amphetamine on DA release from nerve terminals.

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Acknowledgments

These studies were supported by USPHS grants MH066393, MH01245, DA14944, and NS39787. l-Amphetamine was donated by NIH–NIDA/Division of Neuroscience & Behavioral Research. These experiments comply with all laws within the United States of America.

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Authors and Affiliations

  1. Department of Psychiatry, University of Kentucky, 306 Davis Mills Bldg, Lexington, KY, 40536, USA

    Paul E. A. Glaser & Greg A. Gerhardt

  2. Department of Anatomy and Neurobiology, University of Kentucky, 306 Davis Mills Bldg, Lexington, KY, 40536, USA

    Paul E. A. Glaser, Theresa C. Thomas, B. Matthew Joyce & Greg A. Gerhardt

  3. Department of Pediatrics, University of Kentucky, 306 Davis Mills Bldg, Lexington, KY, 40536, USA

    Paul E. A. Glaser

  4. Center for Sensor Technology, University of Kentucky, 306 Davis Mills Bldg, Lexington, KY, 40536, USA

    Theresa C. Thomas, B. Matthew Joyce & Greg A. Gerhardt

  5. Morris K. Udall Parkinson’s Disease Research Center of Excellence, University of Kentucky, 306 Davis Mills Bldg, Lexington, KY, 40536, USA

    Theresa C. Thomas, B. Matthew Joyce & Greg A. Gerhardt

  6. NYU Child Study Center, New York, NY, USA

    F. Xavier Castellanos

  7. Department of Neurology, University of Kentucky, 306 Davis Mills Bldg, Lexington, KY, 40536, USA

    Greg A. Gerhardt

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  1. Paul E. A. Glaser
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  2. Theresa C. Thomas
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  3. B. Matthew Joyce
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Correspondence to Paul E. A. Glaser.

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Glaser, P.E.A., Thomas, T.C., Joyce, B.M. et al. Differential effects of amphetamine isomers on dopamine release in the rat striatum and nucleus accumbens core. Psychopharmacology 178, 250–258 (2005). https://doi.org/10.1007/s00213-004-2012-6

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  • DOI: https://doi.org/10.1007/s00213-004-2012-6

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