Timing and duration of developmental nicotine exposure contribute to attenuation of the tadpole hypercapnic neuroventilatory response

Abstract

The ability for air-breathing vertebrates to adjust ventilation in response to increased CO2 (hypercapnia) is fundamental to maintaining pH homeostasis. Developmental nicotine exposure has been shown to impair tadpole neuroventilatory responses to hypercapnia following 8-12 wk 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 μg/L of nicotine for 3- or 10-wk durations, either early or late in tadpole development. Correlates of tadpole lung neuroventilation were monitored during normocapnic (1.5 % CO2) and hypercapnic (5 % CO2) 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 wk. Preparations derived from late metamorphic tadpoles failed to respond to hypercapnia after being exposed to nicotine for 10 wk. These results suggest that both the developmental timing and duration of exposure are important when considering nicotine's effect on the hypercapnic neuroventilatory response.

Chronic nicotine and ethanol exposure both disrupt central ventilatory responses to hypoxia in bullfrog tadpoles

“…This was similar to studies looking at the effect of chronic nicotine exposure on hypercapnic ventilation, where early metamorphic tadpoles exhibited an impaired hypercapnic response after 3-wk nicotine exposure, whereas late metamorphic tadpoles required 10-wk exposure to exhibit the same impairment (Brundage and Taylor, 2009). The effects of acute nicotine exposure, however, are opposite in that they increase with bullfrog development (Brundage et al, 2010).…”

“…We have previously shown that 10 wk of nicotine exposure has no effect on normoxic/normocapnic gill neuroventilation nor does it affect the integrity of the isolated bullfrog brainstem lung activity over the duration of the experiment (Taylor et al, 2008; Brundage and Taylor, 2009). Here we see that 10-wk nicotine exposure did have a significant effect on gill burst activity.…”

“…The ethanol concentration varied due to the volatilization from the aquarium water and was equivalent to 0.63–1.88 times the 0.08 g/dL blood alcohol content that is the legal limit of many western countries (Caldeira et al, 2004). We chose 10-wk exposure because that duration of exposure impairs ventilatory responses to hypercapnia in both early and late metamorphic tadpoles (Taylor et al, 2008; Brundage and Taylor, 2009). We sought to determine if responses to hypoxia were affected after the same 10-wk teratogen exposure.…”

“…The developing bullfrog has been used as a model to investigate the ventilatory effects of nicotine and ethanol exposure (Taylor et al, 2008; Brundage and Taylor, 2009; 2010). Use of bullfrog tadpoles is advantageous in providing for precise control of the exposure conditions by eliminating maternal influences.…”

“…Eight to 12 wk of exposure to either 30 µg/L nicotine or 0.10 % ethanol (v/v) disrupts tadpole ventilatory responses to hypercapnia, both in vivo and in isolated brainstem preparations, without affecting baseline ventilation (Taylor et al, 2008). Both the duration and timing of teratogen exposure are determining factors in nicotine-, but not ethanol-induced, hypercapnic impairments; early metamorphic tadpoles show increased vulnerability to nicotine (Brundage and Taylor, 2009). The aim of this study was to determine if the ventilatory impairments elicited by developmental nicotine and ethanol exposure extend to the bullfrog tadpole central HVR.…”