title: Ethanol and acetaldehyde differentially alter extracellular dopamine and serotonin in Aldh2-knockout mouse dorsal striatum: A reverse microdialysis study.
abstract: Dopamine (DA) and serotonin (5-HT) seem to be involved in several of the effects of ethanol (EtOH). Acetaldehyde (AcH), especially in the brain, induces effects that mimic those of EtOH. The purpose of this study was to investigate the effects of local perfusion of EtOH and AcH on extracellular DA and 5-HT in the dorsal striatum of Aldh2-knockout (Aldh2-KO) and wild-type (WT) mice. Aldh2-KO mice were used as a model of aldehyde dehydrogenase 2 deficiency in humans to examine the effects of AcH. Mice were perfused with Ringer's solution (control), EtOH (100, 200, or 500mM) and AcH (100, 200, or 500μM) into the dorsal striatum. Dialysate samples were collected every 5min, and then analyzed with HPLC coupled to an ECD. We found that local perfusion with 500mM EtOH increased extracellular levels of DA (p<0.05) in both Aldh2-KO and WT mice, while 5-HT levels remain unchanged. EtOH at a dose of 200mM also increased DA in WT mice, but this was limited to a 30-40-min time-point. In contrast, perfusion with 200 and 500μM AcH decreased both DA and 5-HT (p<0.05) in Aldh2-KO mice, but this decrease was not found in WT mice at any AcH dose, indicating an effect of AcH on DA and 5-HT levels. There were no genotype effects on the basal levels of DA and 5-HT. These results indicate that high EtOH can stimulate DA, whereas high AcH can depress both DA and 5-HT in the dorsal striatum of mice.
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. Electronic address: jamaldr68@yahoo.com.
authors.forename: Mostofa
authors.initials: M
authors.lastname: Jamal
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ameno
authors.affiliation: Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Miki
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Anesthesiology and Emergency Medicine, Faculty of Medicine, Kagawa University, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Ono
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Takakura
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kumihashi
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kinoshita
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis; D012701:Serotonin / Q000378:metabolism*
chemical_list: D012701:Serotonin; D000431:Ethanol; C515029:ALDH2 protein, mouse; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde; D004298:Dopamine
keywords: Acetaldehyde; Aldh2-KO mice; Dopamine; Ethanol; Reverse microdialysis; Serotonin