BIPHASIC EFFECTS OF BACLOFEN ON PHRENIC MOTONEURONS - POSSIBLE INVOLVEMENT OF 2 TYPES OF GAMMA-AMINOBUTYRIC ACID (GABA) RECEPTORS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 226  (2) , 616-624
Abstract
Injections of baclofen i.v. have 2 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 .mu.g/kg i.v.) and picrotoxin (900 .mu.g/kg i.v.) restore firing depressed by baclofen, whereas strychnine (80-1280 .mu.g/kg) does not. 3-Aminopropanesulfonic acid (5-75 mg/kg i.v.) an agonist at GABA-A receptor sites, depresses phrenic nerve activity. The low dose stimulatory effects are apparently related to actions at GABA-B receptors, whereas the high dose depressant effects are related, at least in part, to activation of GABA-A receptors.