strychnine and Cough

Cough-related sensory inputs from rapidly adapting receptors (RARs) and C fibers are processed by second-order neurons mainly located in the caudal nucleus tractus solitarii (NTS). Both GABAA and glycine receptors have been proven to be involved in the inhibitory control of second-order cells receiving RAR projections. We investigated the role of these receptors within the caudal NTS in the modulation of the cough reflex induced by either mechanical or chemical stimulation of the tracheobronchial tree in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections (30-50 nl) of the receptor antagonists bicuculline and strychnine as well as of the receptor agonists muscimol and glycine were performed. Bicuculline (0.1 mM) and strychnine (1 mM) caused decreases in peak abdominal activity and marked increases in respiratory frequency due to decreases in both inspiratory time (Ti) and expiratory time (Te), without concomitant changes in arterial blood pressure. Noticeably, these microinjections induced potentiation of the cough reflex consisting of increases in the cough number associated with decreases either in cough-related Ti after bicuculline or in both cough-related Ti and Te after strychnine. The effects caused by muscimol (0.1 mM) and glycine (10 mM) were in the opposite direction to those produced by the corresponding antagonists. The results show that both GABAA and glycine receptors within the caudal NTS mediate a potent inhibitory modulation of the pattern of breathing and cough reflex responses. They strongly suggest that disinhibition is one important mechanism underlying cough regulation and possibly provide new hints for novel effective antitussive strategies.

Topics: Animals; Bicuculline; Cough; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; Glycine; Male; Muscimol; Rabbits; Receptors, GABA-A; Receptors, Glycine; Reflex; Solitary Nucleus; Strychnine

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.

Topics: Animals; Bicuculline; Cough; Male; Pentobarbital; Picrotoxin; Rats; Rats, Inbred Strains; Receptors, GABA-A; Reflex; Respiration; Strychnine

Topics: Animals; Atropine; Cough; Dogs; Glottis; Respiration; Stimulation, Chemical; Strychnine; Trachea