It has been suggested that the facilitation of the GABAergic transmission in­duced by benzodiazepines plays an important role in the antistress and antianxiety effects of these drugs (4,7,35). On the basis of this hypothesis, we evaluated whether anxiolytic benzodiazepine receptor ligands were able to antagonize the decrease in the density of low affinity GABA receptors induced by electrical foot-shock stress in rats. As shown in Table 3, the in vitro addition of diazepam (5 mM to cortical membrane preparations from foot-shocked rats increased the density of low affinity GABA receptors to the level found in nonstressed animals. This finding indicates that in the rat cerebral cortex, benzodiazepine receptors are functionally linked to the low affinity GABA receptors and may play a critical role in the regulation of emotional states. Recently, a novel series of b-carboline derivatives with pharmacological prop­erties opposite to those of anxiogenic b-carbolines have been synthetized. Among

these compounds ethyl-6 benziloxy-4 methoxymethyl-b-carboline-3-carboxylate (ZK 93423) and ethyl 5-benziloxy-4-methoxymethyl-b-carboline-3-carboxylate (ZK 91296) have been characterized as a full and a partial agonist at the ben­zodiazepine receptor, respectively (20,28,32,33). In fact, the activation of ben­zodiazepine receptors induced by these drugs produces anxiolytic and anticon­vulsant effects. Consistent with their benzodiazepine-like profile, the in vitro addition of these anxiolytic b-carbolines to cortical membrane preparations from stressed rats increased in a concentration-dependent fashion the binding of 3 H-GABA to low affinity GABA receptors. This effect, similarly to that of diazepam, was reversed by the addition of the benzodiazepine receptor antagonist Rol5-1788 (Table 3). Altogether these results suggest that these b-carboline derivatives, like ben­zodiazepines, exert their antistress and antianxiety effects by enhancing the GA-BAergic transmission at the level of the GABA/benzodiazepine receptor complex.

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