Involvement of GABAB receptor systems in action of antidepressants. II: Baclofen attenuates the effect of desipramine whereas muscimol has no effect in learned helplessness paradigm in rats.
Involvement of GABAergic systems in action of antidepressants was examined in the learned helplessness paradigm in rats. Rats were treated with desipramine, baclofen or muscimol for 14 days. On day 14, the rats were subjected to 90 inescapable shocks. On day 15, the rats received the 40-trial escape test. The inescapable shocks induced the subsequent increase in escape failures in the escape test. Desipramine dose-dependently improved the increased escape failures induced by the inescapable shocks. Baclofen attenuated the escape failures-improving effect of desipramine, although baclofen had no effects on the increased escape failures when it was injected alone. Muscimol at any dose failed to influence the increased escape failures. Therefore, it is suggested that the long-term decrease in GABAB neurotransmission may be involved in the action of antidepressants. Our present results do not support the hypothesis that activation of GABAA receptors may contribute to the action of antidepressants.
Nakagawa
Y
Y
Tsukuba Research Laboratories, Experimental Biomedical Research Inc. (Jisseiken), Ibaraki, Japan.
Ishima
T
T
Ishibashi
Y
Y
Tsuji
M
M
Takashima
T
T
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001418:Baclofen / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006380:Helplessness, Learned; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000928:Antidepressive Agents; D009118:Muscimol; D001418:Baclofen; D003891:Desipramine