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Neuroventilation is highly plastic and exposure to either of two distinct teratogens, nicotine or ethanol, during development results in a similar loss of the neuroventilatory response to hypercapnia in bullfrog tadpoles. Whether this functional deficit is permanent or transient following nicotine or ethanol exposure was unknown. Here, we tested the persistence of hypercapnic neuroventilatory response impairments in tadpoles exposed to either 30 microg/L nicotine or 0.12-0.06 g/dL ethanol for 10 weeks. Brainstem breathing-related neural activity was assessed in tadpoles allowed to develop teratogen-free after either nicotine or ethanol exposure. Nicotine-exposed animals responded normally to hypercapnia after a 3-week teratogen-free period but the hypercapnic response in ethanol-exposed tadpoles remained impaired. Tadpoles allowed to develop for only 1 week nicotine free after chronic exposure were unable to respond to hypercapnia. The hypercapnic response of ethanol-exposed tadpoles returned by 6 weeks following chronic ethanol exposure. These findings suggest that some nicotine- and ethanol-induced impairments can be resolved during early development. Understanding both the disruptive effects of nicotine and ethanol exposure and how impaired responses return when teratogen exposure stops may offer insight on the function and plasticity of respiratory control.

Nicotine exposure is associated with numerous neurodevelopmental aberrations, including impairment of the neuroventilatory response to hypercapnia in bullfrog tadpoles and mouse neonates following prolonged developmental exposure. It is unclear how acute nicotine exposure affects neuroventilation and the neuroventilatory response to hypercapnia, or how these effects might differ from those of chronic exposure. In this study the neural correlates of ventilation were recorded from in vitro brainstem preparations derived from early and late metamorphic tadpoles and juvenile bullfrogs. Lung and gill/buccal breath parameters were compared during control (=0), 18, 50, 100, and 200microg/L nicotine conditions, applied during normocapnia (1.5% CO(2)) and hypercapnia (5.0% CO(2)). All preparations demonstrated a reduction in normocapnic lung burst frequency and an attenuated hypercapnic response during acute nicotine treatment. The concentrations necessary to elicit both of these responses decreased from 200microg/L nicotine in early metamorphic tadpole brainstems to 18microg/L nicotine in juvenile bullfrog brainstems, which suggests a developmental increase in acute nicotine sensitivity that is distinguishable from the developmental changes in vulnerability to chronic nicotine exposure. In summary, acute nicotine exposure impaired central CO(2) response, attenuated rather than enhanced respiratory drive, and had more pronounced effects at progressively lower concentrations as development proceeded through metamorphosis., (Copyright 2010 Elsevier B.V. All rights reserved.)

The ability for air-breathing vertebrates to adjust ventilation in response to increased CO(2) (hypercapnia) is fundamental to maintaining pH homeostasis. Developmental nicotine exposure has been shown to impair tadpole neuroventilatory responses to hypercapnia following 8-12 weeks of exposure. It is not clear, however, to what extent the timing of exposure during development and/or the duration over which the exposure takes place contribute to this impairment. Here, tadpoles were exposed to 30 microg/L of nicotine for 3- or 10-week durations, either early or late in tadpole development. Correlates of tadpole lung neuroventilation were monitored during normocapnic (1.5% CO(2)) and hypercapnic (5% CO(2)) conditions of isolated brainstems. Preparations derived from early metamorphic tadpoles failed to increase lung neuroventilation in response to hypercapnia whether they had been exposed to nicotine for 3 or 10 weeks. Preparations derived from late metamorphic tadpoles failed to respond to hypercapnia after being exposed to nicotine for 10 weeks. These results suggest that both the developmental timing and duration of exposure are important when considering nicotine's effect on the hypercapnic neuroventilatory response.

Abstract: Chronic ethanol exposure early in development is deleterious to neural development and may impair responses to ventilatory stimuli (ventilatory drive) that maintain homeostasis. Central hypercapnic ventilatory drive (CHVD) increases ventilation to ensure pH homeostasis and accommodate the metabolic production of CO2. We tested the hypothesis that chronic ethanol exposure impairs CHVD in bullfrog tadpoles. Early and late metamorphic tadpoles were exposed in vivo to 0.12–0.06g/dL ethanol for either 3- or 10-wk durations. Brainstems from these animals were isolated and the neural correlates of ventilation were recorded in vitro during superfusion with normocapnic (1.5% CO2:98.5% O2) and hypercapnic (5.0% CO2:95.0% O2) artificial cerebral spinal fluid. Normocapnic neuroventilation was unaffected by chronic ethanol exposure. The typical response to hypercapnia, an increase in lung burst frequency, was lost following 10 but not 3wk of ethanol exposure in both early and late metamorphic tadpoles. The neuroventilatory effects of chronic ethanol exposure were distinguishable from those of acute central ethanol (0.08g/dL) exposure, which attenuated early metamorphic tadpole normocapnic neuroventilation, but had no effect on tadpole CHVD. Thus, 10wk of ethanol exposure both early and late in metamorphosis impairs CHVD in bullfrog tadpoles. [Copyright &y& Elsevier]

Developmental nicotine exposure has been associated with depressed respiratory responses to hypoxic and hypercapnic conditions. We investigated the effect that chronic and acute nicotine exposure (CNE and ANE, respectively) had on the attenuation of hypoxic and hypercapnic respiratory drive. We measured neural correlates of ventilation from the facial and hypoglossal nerves of the isolated tadpole (Rana catesbeiana) brainstem superfused with artificial cerebrospinal fluid (aCSF). Fictive lung and gill breaths were monitored in response to normoxic/normocapnic conditions as well as in response to hypoxic and hypercapnic conditions. Tadpoles were exposed to nicotine either chronically throughout development (18ng/ml pond water for 10 weeks) or acutely with nicotine superfusion of their brainstem (18ng/ml aCSF for 30 minutes). Both CNE and ANE animals demonstrated neuroventilatory gill ataxia in response to hypoxic and hypercapnic conditions. CNE tadpoles failed to produce a significant fictive lung response to either hypoxic or hypcrcapnic conditions. There was no significant difference between lung responses among ANE and control animals. This would suggest that duration of nicotine exposure influences how that exposure impacts respiratory drive. Implications in Sudden Infant Death Syndrome are discussed. [ABSTRACT FROM AUTHOR]