Involvement of GABA(B) receptor systems in experimental depression: Baclofen but not bicuculline exacerbates helplessness in rats

There are two gamma-aminobutyric acid (GABA) hypotheses of the antidepressants action: an increase in GABA(A) neurotransmission or a decrease in GABA(B) neurotransmission may contribute to action of antidepressants. In this study, involvement of GABA(A) and GABA(B) receptor systems was examined in the learned helplessness paradigm in rats. Rats were injected with bicuculline or baclofen for 14 days. On day 14, the rats were subjected to 15 inescapable shocks. On day 15, they underwent the 40-trial escape test. Baclofen exacerbated the escape failures in the rats subjected to the inescapable shocks, although baclofen had no effects in the animals without shock pre-treatment. Bicuculline failed to influence the escape failures in the rats with the 15-shock pre-treatment. These results suggest that the long-term increase in GABA(B) neurotransmission but not the long-term attenuation of GABA(A) neurotransmission may be related to helplessness in rats.