HYPERALGESIC EFFECT INDUCED BY BARBITURATES, MIDAZOLAM AND ETHANOL - PHARMACOLOGICAL EVIDENCE FOR GABA-A RECEPTOR INVOLVEMENT

The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the b arbiturates phenobarbital (5-50 mg/kg), pentobarbital (17-33 mg/kg), a nd thiopental (7.5-30 mg/kg), of the benzodiazepine midazolam (10 mg/k g) or of ethanol (0.4-1.6 g/kg) administered by the systemic route red uced the latency for the tail-flick response, thus inducing a 'hyperal gesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12-1.0 mg/kg) administered systemicall y induced an increase in the latency for the tail-flick response, ther efore characterizing an 'antinociceptive' state. Previous picrotoxin ( 0.12 mg/kg) treatment abolished the hyperalgesic state induced by effe ctive doses of the barbiturates, midazolam or ethanol. Since phenobarb ital, midazolam and ethanol reproduced the described hyperalgesic effe ct of GABA-A-specific agonists (muscimol, THIP), which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of noci ception in the rat central nervous system.