Influence of developmental nicotine exposure on central respiratory‐related cholinergic neurotransmission in the brainstem spinal cord preparation

Abstract

Developmental nicotine exposure (DNE) is correlated with postnatal breathing disorders, and evidence points to a loss of acetylcholine receptor (AChR) function in brainstem regions that participate in central breathing control. Since ACh is the endogenous ligand for nicotinic (nAChRs) and metabotropic AChRs (m-type AChRs), we test the hypothesis that DNE alters both nAChRs and m-type AChRs. DNE was produced by implanting osmotic minipumps into dams during early gestation. We then recorded respiratory-related C4 ventral root (C4VR) activity in brainstem spinal cord preparations from 0–5 day old rats. Drugs were applied to the medullary compartment of a “split-bath” chamber that separated the medulla from the spinal cord. In control pups, bath application of ACh plus atropine, which isolates nAChRs, increased the frequency of C4VR discharge (129% of baseline), whereas ACh plus curare, which isolates m-type AChRs, reduced frequency by 20%. DNE had no effect on m-type nAChRs, but blunted the C4VR frequency response to stimulation of nAChRs (105% vs.129%), indicating that DNEs affects on respiratory rhythm are mediated solely by nAChRs. Support: NIH R03HD061613-01, AHA 0855713G.