The GABA(B) receptor antagonist CGP36742 improves learned helplessness in rats

Effects of 3-aminopropyl-n-butyl-phosphinic acid (CGP36742), a GABA(B) receptor antagonist, in the learned helplessness paradigm were examined in rats in comparison with those of imipramine and endo-8-methyl-8-azabicyclo[3,2,1]oct-3-ol indol-3-yl-carboxylate hydrochloride (ICS205-930). Rats were treated with CGP36742, imipramine or ICS205-930 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 increased escape failures in the escape test. CGP36742, imipramine and ICS205-930 dose-dependently improved the escape failures induced by the inescapable shocks. Baclofen attenuated the escape failures-improving effect of CGP36742, imipramine and ICS205-930. Although the action of imipramine and ICS205-930 was attenuated by 1-(m-chlorophenyl)-biguanide (mCPBG), mCPBG failed to influence the CGP36742 action. Therefore, it is suggested that CGP36742 may have an antidepressant profile and that the mechanisms of CGP36742 in antidepressant action may be different from those of imipramine and ICS205-930.