Involvement of GABAB 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 GABAA neurotransmission or a decrease in GABAB neurotransmission may contribute to action of antidepressants. In this study, involvement of GABAA and GABAB 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 GABAB neurotransmission but not the long-term attenuation of GABAA neurotransmission may be related to helplessness in rats.