Influence of prenatal nicotine exposure on in vitro central respiratory‐related cholinergic neurotransmission

Abstract

Prenatal nicotine exposure (PNE) is correlated with breathing abnormalities in both humans and other animals. Despite evidence this relationship results from alterations in nicotinic acetylcholine receptors (nAChRs), which mediate vital brain stem respiratory‐related cholinergic neurotransmission, a complete mechanistic understanding is lacking. In the present study, we hypothesize that PNE alters medullary nAChRs, which then leads to a blunted respiratory motor output following acute nAChR excitation. To test this hypothesis, we used an in vitro “split‐bath” brain stem spinal cord preparation and recorded C4 ventral root (C4VR) nerve bursts from 0–4 day old rats. Rats were exposed to either nicotine (6 mg/kg/day) or saline (control) in utero. Results show that following PNE peak C4VR burst frequency in response to bath application of nicotine was decreased 57% at [0.25 ìM] nicotine and 45% at [0.5 ìM] compared to controls. Our results also indicate that á4â2 nAChRs play a dominant role in the nicotine‐induced increase in C4VR burst frequency, since its antagonism completely blocked nicotine's effect on C4VR burst frequency in both PNE and control animals, while á7 antagonism had no effect in either group. These data suggests that the reduction in nicotine‐induced C4VR burst frequency in PNE animals is due to an anatomical and/or functional decrease in excitatory neurotransmission mediated by á4â2 nAChRs.