Abstract
We have previously shown that the caudal ventral respiratory group (cVRG) is a possible site of action of some antitussive drugs and plays a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. In addition, it has been reported that medullary expiratory neurons of the cVRG are subject to potent GABAergic gain modulation. This study was devoted to investigate the role of cVRG GABAA receptors in the control of baseline respiratory activity and cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. To this purpose, bilateral microinjections (30–50 nl) of bicuculline or muscimol were performed into the cVRG of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bicuculline (1 mM) increased peak abdominal activity and respiratory frequency due to decreases in TE. Cough responses were potentiated mainly owing to increases in the cough number. The recovery was observed within ~2 h. On the contrary, muscimol (0.3 mM) abolished abdominal activity and decreased respiratory frequency due to increases in TE. In addition, cough responses were progressively reduced and completely suppressed within ~20 min. Partial recovery of cough responses was achieved after ~3 h or within ~5 min following bicuculline microinjections at the same locations. The sneeze reflex induced by mechanical stimulation of the nasal mucosa persisted following bicuculline and muscimol microinjections. However, the number and intensity of expiratory thrusts were enhanced by bicuculline and suppressed by muscimol. The results provide evidence that a potent GABAA-mediated inhibitory modulation is exerted at the level of the cVRG not only on respiratory activity, but also on cough and sneeze reflex responses.
Highlights
Cough is one of the most important airway defensive reflexes (Korpáš and Tomori, 1979)
We have previously shown that the caudal ventral respiratory group is a possible site of action of some antitussive drugs and plays a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern
The results provide evidence that a potent GABAA-mediated inhibitory modulation is exerted at the level of the caudal ventral respiratory group (cVRG) on respiratory activity, and on cough and sneeze reflex responses
Summary
Cough is one of the most important airway defensive reflexes (Korpáš and Tomori, 1979). The cough reflex is subserved by several central structures (e.g., Kubin and Davies, 1995; Gestreau et al, 1997; Bongianni et al, 1998; Pantaleo et al, 2002; Shannon et al, 2004; Bolser et al, 2006; Bonham et al, 2006; Kubin et al, 2006; Jakuš et al, 2008; Poliacek et al, 2011) including the expiratory neurons of the caudal ventral respiratory group (cVRG) These neurons are involved in the production of both the components of the cough motor pattern, but appear to represent merely an expiratory output system for sneezing (Bongianni et al, 2005; Mutolo et al, 2009). The activation of centrally located GABAB receptors, including those within the cVRG and the caudal aspect of the nucleus tractus solitarii (NTS), has been shown to be involved in the control of the cough reflex (Bolser et al, 1994, 1995; Mutolo et al, 2008b, 2010), no information is available, to our knowledge, on the role of brainstem GABAA receptors in this reflex
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