Proconflict effect of benzodiazepine receptor inverse agonists and other inhibitors of GABA function

Abstract

GABA seems to be a neurotransmitter with great impact on conflict behaviour in rats. We studied the effects of different types of GABA function inhibitors on conflict behaviour in rats. Among these inhibitors, the benzodiazepine (BZ) receptor inverse agonists are a new type of compound downregulating GABA-mediated functions allosterically. The most effective proconflict inducing compounds were pentylenetetrazol and the three BZ inverse agonists β-CCM, β-CCE and ZK 90886. The BZ receptor inverse agonists, FG 7142, DMCM and CGS 8216, the GABA antagonist bicuculline and the GABA synthesis inhibitor isoniazid were moderately active. Only a weak effect was seen with just subconvulsive doses of picrotoxin, a chloride channel inhibitor. These results show that the mode of GABA function inhibition determines the degree to which proconflict action is elicited and that proconflict effects and proconvulsant or convulsant effects may be separated. Evidence is presented that proconflict action in rats is predictive of an anxiogenic action in man.