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.
Original language | English |
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Pages (from-to) | 250-258 |
Number of pages | 9 |
Journal | Psychopharmacology |
Volume | 178 |
Issue number | 2-3 |
DOIs | |
State | Published - Mar 2005 |
Bibliographical note
Funding Information: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.
Keywords
- Amphetamines
- Dopamine
- Nucleus accumbens
- Psychostimulants
- Striatum
- Voltammetry
ASJC Scopus subject areas
- Pharmacology