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

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.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Glaser PE,Thomas TC,Joyce BM,Castellanos FX,Gerhardt GA

doi

10.1007/s00213-004-2012-6

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

250-8

issue

2-3

eissn

0033-3158

issn

1432-2072

journal_volume

178

pub_type

杂志文章

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