PT - JOURNAL ARTICLE AU - P M Lalley TI - Biphasic effects of baclofen on phrenic motoneurons: possible involvement of two types of gamma-aminobutyric acid (GABA) receptors. DP - 1983 Aug 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 616--624 VI - 226 IP - 2 4099 - http://jpet.aspetjournals.org/content/226/2/616.short 4100 - http://jpet.aspetjournals.org/content/226/2/616.full SO - J Pharmacol Exp Ther1983 Aug 01; 226 AB - Intravenous injections of baclofen have two general dose-dependent effects on phrenic motoneurons in anesthetized cats. Small doses (0.5-1.5 mg/kg) increase the frequency of action potentials recorded from single motoneurons and from the phrenic nerve, whereas large doses (2-10 mg/kg) reduce or abolish action potentials. The increase in frequency produced by small doses is accompanied by membrane depolarization and, in most experiments, by increased input resistance. Large doses hyperpolarize phrenic motoneurons and produce greater increases in input resistance. Extracellular recording during microelectrophoretic application of baclofen reveals only one effect, depression of cell firing, at all effective current strengths. The low dose stimulatory effect of i.v. baclofen is attributed to disinhibition, whereas the depression by large doses is attributed to disfacilitation. During incomplete inhibition by baclofen, CO2 administration further depresses phrenic nerve activity. Bicuculline (100-600 micrograms/kg i.v.) and picrotoxin (900 micrograms/kg i.v.) restore firing depressed by baclofen, whereas strychnine (80-1280 micrograms/kg) does not. 3-Aminopropanesulfonic acid (5-75 mg/kg i.v.) an agonist at gamma-aminobutyric acid-A receptor sites, depresses phrenic nerve activity. It is suggested that the low dose stimulatory effects are related to actions at gamma-aminobutyric acid-B receptors, whereas the high dose depressant effects are related, at least in part, to activation of gamma-aminobutyric acid-A receptors.