, Volume 178, Issue 2–3, pp 250–258 | Cite as

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

  • Paul E. A. Glaser
  • Theresa C. Thomas
  • B. Matthew Joyce
  • F. Xavier Castellanos
  • Greg A. Gerhardt
Original Investigation



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.


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.


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.


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.


Amphetamines Psychostimulants Dopamine Voltammetry Striatum Nucleus accumbens 



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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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Paul E. A. Glaser
    • 1
    • 2
    • 3
  • Theresa C. Thomas
    • 2
    • 4
    • 5
  • B. Matthew Joyce
    • 2
    • 4
    • 5
  • F. Xavier Castellanos
    • 6
  • Greg A. Gerhardt
    • 1
    • 2
    • 4
    • 5
    • 7
  1. 1.Department of PsychiatryUniversity of KentuckyLexingtonUSA
  2. 2.Department of Anatomy and NeurobiologyUniversity of KentuckyLexingtonUSA
  3. 3.Department of PediatricsUniversity of KentuckyLexingtonUSA
  4. 4.Center for Sensor TechnologyUniversity of KentuckyLexingtonUSA
  5. 5.Morris K. Udall Parkinson’s Disease Research Center of ExcellenceUniversity of KentuckyLexingtonUSA
  6. 6.NYU Child Study CenterNew YorkUSA
  7. 7.Department of NeurologyUniversity of KentuckyLexingtonUSA

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