Acetyl-L-carnitine releases dopamine in rat corpus striatum: an in vivo microdialysis study.
The effect of acetyl-L-carnitine, a compound reported to be beneficial for senile patients, on the release of dopamine (DA) from the striatum was studied by using in vivo brain dialysis in anesthetized rats coupled with HPLC-electrochemical detection. Striatal infusion of acetyl-L-carnitine increased the efflux of DA with no apparent changes in efflux of DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA). The DA-releasing effect of acetyl-L-carnitine was concentration- and Ca(2+)-dependent, and was abolished by omega-conotoxin fraction GVIA and tetrodotoxin, inhibitors of the voltage-dependent Ca2+ and Na+ channels, respectively. Nomifensine, an inhibitor of DA reuptake did not alter the DA-releasing property of acetyl-L-carnitine. DA released from the striatum by acetyl-L-carnitine was decreased by reserpine pretreatment whereas the d-amphetamine-evoked DA outflow was not affected. In contrast to acetyl-L-carnitine, d-amphetamine reduced the extracellular concentrations of DOPAC and HVA. We conclude from the present data that acetyl-L-carnitine evokes DA release from the vesicular pools of the nigrostriatal dopaminergic neurons by a Ca(2+)-dependent, exocytotic process.
Harsing
L G
LG
Center for Neurochemistry, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962.
Sershen
H
H
Toth
E
E
Hashim
A
A
Ramacci
M T
MT
Lajtha
A
A
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D005089:Exocytosis; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D009627:Nomifensine; D000108:Acetylcarnitine; D002118:Calcium; D003913:Dextroamphetamine; D004298:Dopamine