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 grey region), progabide (a GABA agonist) and diazepam both increased the latency to escape to a safe compartment and also the current needed to induce the escape response (escape threshold). Furthermore, the effects of progabide and diazepam were greater than additive in their actions on the escape response as when given together in normally subliminal doses, the combination exerted a marked anti-aversive effect. These actions of the drugs alone or in combination could not be explained by non-specific motor effects. Blockade of GABA receptors by bicuculline greatly reduced or abolished the action of progabide and diazepam (single administration). Sodium valproate, which indirectly augments GABAergic transmission, also increased the escape latency and escape threshold whereas, in contrast, diphenylhydantoin accentuated the aversive effects of stimulation of the periaqueductal grey. 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. These results are interpreted as an indication that GABA agonists have an anti-aversive action in this proposed rat model for anxiety and, furthermore, that GABA receptors at least partially mediate the actions of benzodiazepines in this model.
D000818:Animals; D014151:Anti-Anxiety Agents; D001007:Anxiety / Q000188:drug therapy*; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004347:Drug Interactions; D004558:Electric Stimulation; D004924:Escape Reaction / Q000187:drug effects*; D006801:Humans; D008297:Male; D010487:Periaqueductal Gray / Q000187:drug effects*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000502:physiology* / Q000627:therapeutic use
D014151:Anti-Anxiety Agents; C017985:progabide; D005680:gamma-Aminobutyric Acid; D003975:Diazepam