Prenatal nicotine exposure with continued exposure through breast milk over the first week of life (developmental nicotine exposure, DNE) alters the development of brainstem circuits that control breathing. Here, we test the hypothesis that DNE alters the respiratory motor response to endogenous and exogenous acetylcholine (ACh) in neonatal rats. We used the brainstem-spinal cord preparation in the split-bath configuration, and applied drugs to the brainstem compartment while measuring the frequency and amplitude of the fourth cervical ventral nerve roots (C4VR), which contain the axons of phrenic motoneurons. We applied ACh alone; the nicotinic acetylcholine receptor (nAChR) antagonist curare, either alone or in the presence of ACh; and the muscarinic acetylcholine receptor (mAChR) antagonist atropine, either alone or in the presence of ACh. The main findings include: 1) atropine reduced frequency similarly in controls and DNE animals, while curare caused modest slowing in controls but no consistent change in DNE animals; 2) DNE greatly attenuated the increase in C4VR frequency mediated by exogenous ACh; 4) stimulation of nAChRs with ACh in the presence of atropine increased frequency markedly in controls, but not DNE animals; 5) stimulation of mAChRs with ACh in the presence of curare caused a modest increase in frequency, with no treatment group differences. DNE blunts the response of the respiratory central pattern generator to exogenous ACh, consistent with reduced availability of functionally competent nAChRs; DNE did not alter the muscarinic control of respiratory motor output.
Prenatal nicotine exposure with continued exposure through breast milk over the first week of life (developmental nicotine exposure, DNE) alters development of the brainstem circuits that control breathing. Previous work has shown that DNE desensitizes nicotinic acetylcholine receptors (nAChRs) and alters the respiratory motor response to exogenous nicotine in neonatal rats. In the brainstem‐spinal cord (BSSC) split‐bath preparation, nicotine applied to the medullary compartment increases the frequency of respiratory related bursting recorded from the fourth cervical ventral root (C4VR), but this effect is markedly blunted by DNE. Because ACh is the endogenous ligand for both nAChRs and muscarinic acetylcholine receptors (mAChRs), and mAChRs are expressed on PreBotzinger neurons, we hypothesized that DNE also alters muscarinic modulation of C4VR frequency in this system. In neonatal rats, postnatal day 0‐6, 1 mM muscarine, a mAChR agonist, applied to the medullary compartment in the BSSC split‐bath preparation increased burst frequency recorded from C4VR in 4/4 control animals and, in some cases, the pattern of bursting became irregular. Muscarine applied to the medulla decreased burst frequency in 4/4 DNE animals. These preliminary data show that chronic stimulation of nAChRs also alters the development of muscarinic synaptic transmission by yet to be determined mechanisms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.