Central CO2 chemosensitivity in tadpoles: impairment and the role of serotonin

Abstract

Nicotine and ethanol are known neuroteratogens and prenatal exposure correlates with Sudden Infant Death Syndrome (SIDS), which is thought to result from failure to maintain pH homeostasis through respiratory adjustments. This failed homeostatic control is believed to be serotonergic in origin. In previous studies nicotine or ethanol exposure ablated the robust hypercapnic response of early-stage tadpoles. These findings lead us to question if the ablation occurred through a serotonindependent mechanism. This study investigated the role of serotonin (5- HT) in the nicotine- or ethanol-induced abolishment of the hypercapnic response. We found that toxin-exposed animals were insensitive to hypercapnia and also failed to respond to concomitant exposure to hypercapnia and 8-OH-DPAT, supporting our hypothesis that toxininduced abolishment of the hypercapnic response is mediated by 5-HTia receptors. Immunofluorescence data from brainstem slices of ethanolexposed animals showed a decrease in 5-HTia receptors and the serotonin-synthesizing enzyme tryptophan hydroxylase. In contrast, 3- wk nicotine-exposed animals displayed no significant difference in immunofluorescence for either protein. Taken together the electrophysiological and immunofluorescence data suggest the effects of ethanol or nicotine exposure, which impair the hypercapnic response, include a failure of serotonergic signaling and that this failure is not simply the reflection of a global reduction in serotonin levels.