Can anti-panic drugs antagonise the anxiety produced in the rat by drugs acting at the GABA-benzodiazepine receptor complex?

The beta-carboline FG 7142 and pentylenetetrazole, believed to act at different sites on the GABA-benzodiazepine receptor complex, have anxiogenic activity in the social interaction test in the rat. Two compounds that have anti-panic activity in man, the tricyclic antidepressant imipramine and the alpha 2-adrenoceptor agonist clonidine, were used to try to antagonise the anxiogenic effects of the 2 drugs. Imipramine (5 and 15 mg/kg) was tested after 0 or 15 days pretreatment. In neither case was it able to reverse the anxiogenic effect of pentylenetetrazole (15 mg/kg). However, after chronic treatment the effects of FG 7142 were reversed. Imipramine itself had an anxiogenic action that was significant after acute treatment, and its effects were not additive with those of FG 7142 or pentylenetetrazole, suggestive of some mutual antagonism between acute imipramine and the 2 drugs. Similar mutual antagonism was obtained after acute treatment with clonidine (0.01 and 0.025 mg/kg).