[abstract] FACILITATION OF GABA TRANSMISSION OPPOSES THE HPNS

Abstract

Recent studies in this laboratory have demonstrated that facilitation of GABA transmission does oppose the hyperexcitability of the HPNS. We have shown that four drugs which increase GABA transmission in different ways are effective against the behavioural signs of the HPNS in mice. Sodium valproate and the benzodiazepine, flurazepam, each raised the onset pressures for tremors and for convulsions by 40-7PbAminooxyacetic acid and diaminobutyric acid each raised these onset pressures by 20-3%. The effects of flurazepam were completely antagonised by the benzodiazepine antagonist Ro 15-1788, which had no effect alone. This showed that the effects of flurazepam were due to its interaction with benzodiazepine receptors, which are linked with GABA receptors, rather than to nonspecific effects. In order to study the effects of pressure on postsynaptic responses to GABA we have adapted the method of Brown and Marsh for extracellular recording from the rat superior cervical ganglion in vitro. ZI contrast to the depression of nicotinic responses seen at 130 atm helium (and reported by other workers), this pressure did not alter the postsynaptic actions of GABA (thought to be due to increased chloride permeability). Dose dependent effects of anaesthetics, for example N20 and ketamine, were seen on these postsynaptic responses. Nicotinic responses were depressed but those to GABA were increased at low concentrations and depressed at high concentrations of anaesthetic. These effects were not altered by the application of 130atm helium. We have shown that drugs which selectively increase the level of GABA activity in the CNS decrease the hyperexcitability effects of helium pressure. We suggest in addition that facilitation of GABA transmission may be a contributing factor in the effectiveness of general anaesthetics, in addition to their nonspecific actions.