In vivo study of salsolinol produced by a high concentration of acetaldehyde in the striatum and nucleus accumbens of free-moving rats.
BACKGROUND
Salsolinol, a neuropharmacologically active compound, is formed by the condensation of acetaldehyde (AcH) with dopamine (DA) in the brain. The aim of our study was to examine the effect of a high concentration of AcH on salsolinol formation and to compare the release of DA, serotonin (5-HT), and salsolinol in the striatum and nucleus accumbens (NAc) in free-moving rats.


METHODS
After the insertion of a microdialysis probe, male Wistar rats (250-300 g) were treated with cyanamide (CY, a potent aldehyde dehydrogenase inhibitor) + ethanol (EtOH), CY + 4-methylpyrazole (4-MP, a strong alcohol dehydrogenase inhibitor) + EtOH, 4-MP + EtOH, CY, and 4-MP. Simultaneous quantitation of DA, 5-HT, and salsolinol in dialysates was performed by using in vivo microdialysis coupled with high-performance liquid chromatography with an electrochemical detector and blood EtOH and AcH by using a head-space gas chromatographic method.


RESULTS
Salsolinol was detected only in the CY + EtOH groups in both the striatum and NAc, and we also detected a high AcH concentration in the blood in those groups. A correlation was found between the dialysate levels of salsolinol and blood concentrations of AcH. The striatal levels of DA and 5-HT were approximately two times higher, whereas salsolinol levels were approximately three times higher compared with the usual level in the NAc. No significant difference of DA and 5-HT levels in the dialysates was observed in either the control or the other study groups.


CONCLUSIONS
Our observation suggested that the brain salsolinol formation may depend on the concentrations of DA and AcH in freely moving rats, and there is no effect of a high concentration of AcH on DA and 5-HT levels in the striatum and NAc.
Jamal
Mostofa
M
Department of Forensic Medicine, Faculty of Medicine, Kagawa Medical University, Ikenobe, Miki, Kita, Kagawa, Japan. jamal@kms.ac.jp
Ameno
Kiyoshi
K
Ameno
Setsuko
S
Okada
Naoko
N
Ijiri
Iwao
I
D000079:Acetaldehyde / Q000633:toxicity*; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003484:Cyanamide / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D000077604:Fomepizole; D007546:Isoquinolines / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism
D007546:Isoquinolines; D011720:Pyrazoles; D012701:Serotonin; D000431:Ethanol; D003484:Cyanamide; D000077604:Fomepizole; C036617:salsolinol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D004298:Dopamine