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


OBJECTIVE
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.
Glaser
Paul E A
PE
Department of Psychiatry, University of Kentucky, 306 Davis Mills Bldg, Lexington, KY 40536, USA. pglas0@uky.edu
Thomas
Theresa C
TC
Joyce
B Matthew
BM
Castellanos
F Xavier
FX
Gerhardt
Greg A
GA
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D064699:Dexmethylphenidate Hydrochloride; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D008297:Male; D008774:Methylphenidate / Q000031:analogs & derivatives / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects*; D019998:Racemases and Epimerases; D051381:Rats; D011916:Rats, Inbred F344; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C090411:Adderall; D000662:Amphetamines; D000697:Central Nervous System Stimulants; D064699:Dexmethylphenidate Hydrochloride; D008774:Methylphenidate; D019998:Racemases and Epimerases; D004298:Dopamine
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