Potential antidepressant properties of subchronic GABA transaminase inhibitors in the forced swimming test in mice.
We carried out the forced swimming test in mice to investigate the antidepressant potentials of GABA transaminase (GABA-T) inhibitors including aminooxyacetic acid, ethanolamine-O-sulfate, gamma-vinyl GABA (GVG) and valproic acid (VPA). In acute experiments only GVG reduced immobility. Following chronic oral administration via drinking water containing the drugs, immobility was significantly reduced at days 5 and 10 in all of the GABA-T inhibitors examined. The tolerance of the anti-immobility effect, however, occurred at day 20. Brain GABA contents showed moderate to marked increase during the session with the exception of VPA, which did not alter GABA contents. These results suggest that subchronic GABA-T inhibitors possess antidepressant properties, though the anti-immobility effect of GABA-T inhibitors did not directly correlate with the increase in brain GABA.
Semba
J
J
Department of Neuropsychiatry, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Kuroda
Y
Y
Takahashi
R
R
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000614:Aminocaproates / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents; D004353:Drug Evaluation, Preclinical; D004983:Ethanolamines / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects; D013550:Swimming; D014635:Valproic Acid / Q000494:pharmacology; D020888:Vigabatrin
D000614:Aminocaproates; D000928:Antidepressive Agents; D004983:Ethanolamines; D011963:Receptors, GABA-A; D000625:Aminooxyacetic Acid; D014635:Valproic Acid; C020619:ethanolamine O-sulfate; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin