Nicotine elicits a developmentally dependent depression in bullfrog neuroventilatory response to CO2

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 200 μg/L nicotine conditions, applied during normocapnia (1.5% CO2) and hypercapnia (5.0% CO2). 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 200 μg/L nicotine in early metamorphic tadpole brainstems to 18 μg/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 CO2 response, attenuated rather than enhanced respiratory drive, and had more pronounced effects at progressively lower concentrations as development proceeded through metamorphosis.