Respiratory responses induced by blockades of GABA and glycine receptors within the Botzinger complex and the pre-Botzinger complex of the rabbit

The respiratory role of GABA(A), GABA(B) and glycine receptors within the Botzinger complex (BotC) and the pre-Botzinger complex (preBotC) was investigated in a-chloralose-urethane anesthetized, vagotomized, paralysed and artificially ventilated rabbits by using bilateral microinjections (30-50 nl) of GABA and glycine receptor agonists and antagonists. GABA(A) receptor blockade by bicuculline (5 mM) or gabazine (2 mM) within the BotC induced strong depression of respiratory activity up to apnea. The latter was reversed by hypercapnia. Glycine receptor blockade by strychnine (5 mM) within the MAC decreased the frequency and amplitude of phrenic bursts. Bicuculline microinjections into the preBotC caused decreases in respiratory frequency and the appearance of two alternating different levels of peak phrenic activity. Strychnine microinjections into the preBotC increased respiratory frequency and decreased peak phrenic amplitude. GABA(A), but not glycine receptor antagonism within the preBotC restored respiratory rhythmicity during apnea due to bicuculline or gabazine applied to the BotC. GABA(B) receptor blockade by CGP-35348 (50 mM) within the BotC and the preBotC did not affect baseline respiratory activity, though microinjections of the GABA(B) receptor agonist baclofen (1 mM) into the same regions altered respiratory activity. The results show that only GABA(A) and glvcine receptors within the BotC and the preBotC mediate a potent control on both the intensity and frequency of inspiratory activity during eupneic breathing. This study is the first to provide evidence that these inhibitory receptors have a respiratory function within the BotC. (C) 2010 Elsevier B.V. All rights reserved.