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The effects of chronic nicotine exposure on chemosensitivity of medullary 5‐HT neurons
Author(s) -
Avraam Joanne,
Wu Yuanming,
Richerson George B
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1090.8
Subject(s) - nicotine , endocrinology , medicine , glutamate receptor , acidosis , brainstem , neuron , chemistry , anesthesia , pharmacology , receptor , biology , neuroscience
5‐HT neurons are chemoreceptive and involved in respiratory control. SIDS has been linked to brainstem 5‐HT abnormalities, fetal nicotine exposure and impaired responses to changes in O 2 and CO 2 . We tested the hypothesis that nicotine may increase the risk of SIDS by impairing 5‐HT neuronal function. We used perforated patch clamp to record changes in firing rate (FR) in response to acidosis and to acute nicotine exposure of 5‐HT neurons cultured for >12 days from the medullary raphé of 2 day old mice. An osmotic minipump was implanted into pregnant mice at E10 supplying 6 or 60 mg kg −1 day −1 of nicotine, and/or nicotine was subsequently added to the cultures at 0.05 μM or 0.5 μM respectively. Neurons were bathed in aCSF at 5% CO 2 (pH 7.4) containing GABA and glutamate receptor blockers until FR stabilized at 1 Hz, then were exposed to two‐ 3 min episodes of 9% CO 2 (pH 7.2) with wash out each time. This was then repeated with aCSF containing 10μM nicotine. Neurons exposed chronically to nicotine (n=92) exhibited a reduced response to acute nicotine exposure and to acidosis. These effects were found to be attributed to both prenatal and postnatal exposure and were more pronounced in mature neurons and in neurons exposed to a higher dose of nicotine. In the developing neonate such changes in 5‐HT neuronal function and chemoreception may impair responses to changes in O 2 and CO 2 and potentially increase the incidence of SIDS.