ENHANCING GABAERGIC TRANSMISSION REVERSES THE AVERSIVE STATE IN RATS INDUCED BY ELECTRICAL-STIMULATION OF THE PERIAQUEDUCTAL GREY REGION

In a proposed rat model for anxiety (electrical stimulation of the periaqueductal gray region), progabide (a GABA agonist) and diazepam increased both the latency to escape to a safe compartment and the amount of current needed to induce the escape response (escape threshold). The effects of progabide and diazepam were greater than additive in their actions on the escape response as when given in normally subliminal doses, the combination exerted a marked antiaversive effect. These actions of the drugs alone or in combination could not be explained by nonspecific motor effects. Blockade of GABA receptors by bicuculline greatly reduced or abolished the action of progabide and diazepam (single administration). Sodium valporate, which indirectly augments GABAergic transmission, also increased the escape latency and escape threshold, diphenylhydantoin accentuated the aversive effects of stimulation of the periaqueductal gray. Haloperidol increased the escape latency and threshold but not other signs of distress following central stimulation (vocalization, jumping) which were effectively blocked by progabide and diazepam. The action of haloperidol was completely explicable by an interference with motor mechanisms. GABA agonists have an antiaversive action in this proposed rat model for anxiety, and GABA receptors may have partially mediate the actions of benzodiazepines in this model.