Effects of GABA antagonists on the pentobarbital-induced depression of respiration and cough in rats

Abstract

In order to determine the possible involvement of GABA-ergic mechanisms in the modulation of the cough reflex, the effects of GABA antagonists on the pentobarbital-induced depression of respiration and cough were examined in a comparative study in rats. The cough reflex was induced by application of electrical stimulation to the tracheal mucosa by the puncture electrode-induced cough method. The 50% antitussive dose (AtD50) of pentobarbital was calculated by the "up and down" method. Pentobarbital (10 mg/kg, IP) caused a reduction of tidal volume, which was counteracted by pretreatment with picrotoxin (3 mg/kg, IP) or bicuculline (3 mg/kg, IP). However, neither picrotoxin nor bicuculline were able to counteract the reduction in frequency of respiration. The AtD50 of pentobarbital was 1.95 mg/kg when administered IP. The AtD50 of pentobarbital was not altered after pretreatment of rats with picrotoxin (1.85 mg/kg, IP) or with bicuculline (1.55 mg/kg). These results suggest that GABA-ergic mechanisms may not be involved in the cough-depressant effect of pentobarbital.