Effects of GABAB receptor ligands in rodent tests of anxiety-like behavior

GABAergic hypothesis of anxiety was introduced many years ago, however, a limited number of supporting data were accumulated so far and the role of GABA(B) receptors in behavioral processes related to the anxiety disorders has not been resolved. In the present study, we examined anxiolytic activity of CGP 36742, a potent and selective GABA(B) receptor antagonist, in rodent tests/models. We have demonstrated that CGP 36742 (30 mg/kg) is active in several animal tests detecting anxiolytic activity (the elevated plus-maze, conflict drinking test and four-plate test). Moreover, we examined the effects of another antagonist--CGP51176 and agonist--CGP 44532 of GABA(B) receptor in the four-plate test in mice. CGP 51176 (5 or 8 mg/kg) was inactive, while CGP 44532 (0.125 mg/kg) exhibited anxiogenic-like effect. These preclinical data further implicate GABA(B) receptor function in anxiety, and support the GABAergic hypothesis of this disorder.