title: Chronic nicotine and ethanol exposure both disrupt central ventilatory responses to hypoxia in bullfrog tadpoles.
abstract: The central hypoxic ventilatory response (HVR) comprises a reduction in ventilatory activity that follows a peripherally mediated ventilatory augmentation. Chronic early developmental exposure to nicotine or ethanol are both known to impair the peripherally mediated HVR, and nicotine impairs the central HVR, but the effect of ethanol on the central HVR has not been investigated. Additionally, chronic nicotine and ethanol exposure are known to impair ventilatory responses to hypercapnia in bullfrog tadpoles but HVRs have not been tested. Here early and late metamorphic tadpoles were exposed to either 30 μg/L nicotine or 0.15-0.05 g/dL ethanol for 10 wk. Tadpole brainstems were then isolated and the neurocorrelates of ventilation were monitored in vitro over 180 min of hypoxia (PO2=5.05±1.04 kPa). Both nicotine and ethanol exposure disrupted central HVRs. Nicotine impairments were dependent on development. Central HVRs were impaired only in early metamorphic nicotine-exposed tadpoles. Both early and late metamorphic ethanol-exposed tadpoles failed to exhibit central HVRs. Thus, central HVRs are impaired following both nicotine and ethanol exposure. Such failure to decrease ventilatory activity during hypoxia indicates that central hypoxic ventilatory depression is an active suppression of neural activity in response to hypoxia rather than a metabolic consequence of O2 limitation, and that exposure to ethanol (across development) or nicotine (during early development) disrupts mechanisms that normally induce active ventilatory depression.
authors.affiliation: Institute of Arctic Biology and Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK 99775-7000, USA. betaylor@alaska.edu
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Taylor
authors.forename: Cord M
authors.initials: CM
authors.lastname: Brundage
authors.forename: Lisa H
authors.initials: LH
authors.lastname: McLane
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005154:Facial Nerve / Q000187:drug effects / Q000503:physiopathology; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011892:Rana catesbeiana; D015656:Respiratory Mechanics / Q000187:drug effects*; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D018722:Nicotinic Agonists; D000431:Ethanol; D009538:Nicotine