Characterization of the in vivo action of (R)-salsolinol, an endogenous metabolite of alcohol, on serotonin and dopamine metabolism: a microdialysis study.
Using a microdialysis-HPLC technique in conscious rats, we examined the action of (R)-1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, (R)-salsolinol (R-Sal), a possible endogenous metabolite of alcohol, on serotonin (5-HT) and dopamine (DA) metabolism in four regions of the brain: the striatum, the substantia nigra, the hippocampus and the hypothalamus. Following 1 mM R-Sal perfusion, the dialysate level of 5-HT in the striatum markedly increased from non-detectable levels to 4259.2 +/- 617.5 nM, while DA increased from 3.4 +/- 0.9 nM to 206.0 +/- 56.5 nM. This increase was one order of magnitude larger in 5-HT than in DA. Conversely, the output of 5-hydroxyindoleacetic acid decreased markedly to non-detectable levels, while 3,4-dihydroxyphenylacetic acid and homovanillic acid outputs decreased below 40% of basal levels. These effects were dose-related to R-Sal (1 microM to 1 mM) and were confirmed also in 3 other brain regions. The R-Sal-induced responses in the striatum were observed even after pretreatment of 2 microM tetrodotoxin, a blocker of nerve-firing activity, via the dialysis membrane. The repetitive perfusion with 1 mM R-Sal into the striatum induced the reproducible response of 5-HT and DA. Furthermore, the potencies of 1 mM R-Sal to increase the output of 5-HT and DA were approximately 783.0-fold and 2.6-fold stronger, respectively, than those of the same dose of methamphetamine. The results suggest that R-Sal acts to stimulate a release of monoamines, 5-HT preferentially, with inhibition of monoamine oxidase and catechol-O-methyltransferase activities.
Nakahara
D
D
Department of Psychology, Nagoya University College of Medical Technology, Japan.
Maruyama
W
W
Hashiguti
H
H
Naoi
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D000431:Ethanol / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology
D015306:Biogenic Monoamines; D002395:Catecholamines; D007546:Isoquinolines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D000431:Ethanol; D008694:Methamphetamine; C036617:salsolinol; D004298:Dopamine