Mostofa Jamal, Asuka Ito, Takanori Miki, Shingo Suzuki, Ken-Ichi Ohta and Hiroshi Kinoshita : Ethanol concentration induces production of 3,4-dihydroxyphenylacetic acid and homovanillic acid in mouse brain through activation of monoamine oxidase pathway., Neuroscience Letters, Vol.782, 2022.
(要約)
First, we aimed to investigate ex vivo the effects of ethanol (EtOH) on levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and their metabolites in the frontal cortex, hippocampus, and striatum of Aldh2-knockout (Aldh2-KO) and wild-type (WT) mice. Animals were treated intraperitoneally with saline (control) or EtOH (1.0, 2.0, or 3.0g/kg). Brain samples were collected 60 and 120min after EtOH injection, and monoamines and their metabolites were measured by HPLC-ECD. We found in both WT and Aldh2-KO mice that 3.0g/kg EtOH increased the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and decreased the level of 3-methoxytyramine (3-MT). A 2.0g/kg dose of EtOH also increased HVA, but there was not a consistent effect within the brain regions of Aldh2-KO and WT mice. There were inconsistent findings of genotype differences in the levels of DA, 5-HT, and their metabolites in the brain regions tested. None of the EtOH doses altered NE, DA, 5-HT, or 5-hydroxyindoleacetic acid contents in any of the brain regions studied. Second, we tested whether EtOH-induced increases in DOPAC and HVA are mediated by increased monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT) activity. To test this, we used the MAO blocker clorgyline (2.0 and 4.0mg/kg) and the COMT blocker tolcapone (15 and 30mg/kg) alone or in combination with EtOH (3.0g/kg). Clorgyline alone increased 3-MT and decreased DOPAC and HVA levels, whereas tolcapone alone increased DOPAC and decreased 3-MT and HVA levels. Surprisingly, the combination of EtOH with clorgyline (4.0mg/kg) or tolcapone (30mg/kg) further decreased 3-MT and increased DOPAC and HVA levels, an effect that reversed the inhibitor-induced decreases in HVA. These results suggest that a high concentration of EtOH can accelerate DA metabolism, as evidenced by the increase in DOPAC and HVA, and this effect is likely a consequence of increased degradation of DA by MAO.
Hiroshi Kinoshita, Naoko Tanaka, Mitsuru Kumihashi, Mostofa Jamal, Asuka Ito, Tadayoshi Yamashita and Kiyoshi Ameno : Fatal poisoning case involving drug interaction due to the inhibition of cytochrome P450, Vojnosanitetski Pregled, Vol.78, No.5, 563-566, 2021.
Mostofa Jamal, Asuka Ito, Naoko Tanaka, Kiyoshi Ameno and Hiroshi Kinoshita : High ethanol and acetaldehyde decrease extracellular glutamate in the frontal cortex of freely moving mice., NeuroReport, 2020.
Mostofa Jamal, Asuka Ito, Naoko Tanaka, Takanori Miki, Kiyoshi Ameno and Hiroshi Kinoshita : High Ethanol and Acetaldehyde Inhibit Glutamatergic Transmission in the Hippocampus of Aldh2-Knockout and C57BL/6N Mice: an In Vivo and Ex Vivo Analysis., Neurotoxicity Research, Vol.37, No.3, 702-713, 2020.
Asuka Ito, Mostofa Jamal, Kiyoshi Ameno, Naoko Tanaka, Ayaka Takakura, Toshihiro Kawamoto, Kyoko Kitagawa, Keiichi Nakayama, Akiko Matsumoto, Takanori Miki and Hiroshi Kinoshita : Acetaldehyde administration induces salsolinol formation in vivo in the dorsal striatum of Aldh2-knockout and C57BL/6N mice., Neuroscience Letters, Vol.685, 50-54, 2018.
(要約)
Acetaldehyde (AcH) and salsolinol play important roles in the central effects of ethanol. This study aimed to investigate the effect of administration of AcH on dopamine (DA), DA-derived salsolinol and serotonin (5-HT) levels in the dorsal striatum of Aldh2-knockout (Aldh2-KO) and C57BL/6N (WT) mice. Animals were treated with AcH (50, 100 and 200mg/kg) intraperitoneally and dialysate levels of DA, 5-HT and salsolinol were determined using in vivo microdialysis coupled with HPLC-ECD. Salsolinol was first detected at 20min after AcH administration, and reached its peak concentration (WT mice: 0.29±0.22pg/μl; Aldh2-KO mice: 0.63±0.17pg/μl) at 25min in the 200mg/kg AcH group, before decreasing rapidly and reaching zero at approximately 55-80min. Treatment with 100 and 200mg/kg AcH increased levels of salsolinol in both WT and Aldh2-KO mice, with 200mg/kg AcH inducing a higher level of salsolinol in Aldh2-KO mice than in WT mice. Treatment with 50mg/kg AcH produced a small increase in salsolinol levels in Aldh2-KO mice, whereas no elevation of salsolinol was detected in WT mice. The increase in salsolinol formation was found to occur a dose-dependent manner in both genotypes. Administration of AcH and the subsequent changes in salsolinol concentrations did not change DA or 5-HT levels in either genotype. Our study suggests that AcH dose-dependently increases the formation of salsolinol in the dorsal striatum of mice, which provides further support for the role of AcH in salsolinol formation in the animal brain.