Parental and larval exposure to nicotine modulate spontaneous activity as well as cholinergic and GABA receptor expression in adult C. elegans

• Increased overall motor activity following parental and larval exposure to nicotine
• Putative presynaptic effect of larval exposure to nicotine supported by increased upstream GABA receptor expression
• Decreased nicotine responsiveness following zygote exposure
• Decreased cholinergic and GABAergic receptor expression resulting from zygote nicotine exposure

Early nicotine exposure has been associated with many long-term consequences that include neuroanatomical alterations, as well as behavioral and cognitive deficits. To describe the effects of early nicotine exposure in Caenorhabditis elegans, the current study observed spontaneous locomotor activity (i.e., reversals) either in the presence or absence of nicotine. Expression of acr-16 (a nicotinic receptor subunit) and a β-like GABAA receptor subunit, gab-1, were also examined with RT-PCR. Worms were exposed to nicotine (30 μM) throughout “zygote formation” (period that includes oocyte maturation, ovulation and fertilization), from hatching to adulthood (“larval development”) or across both zygote and larval development. Adult larval-exposed worms only showed an increase in spontaneous behavior when tested on nicotine (p < 0.001) but levels of activity similar to controls when tested on plain plates (p > 0.30). Larval-exposed worms also showed control levels of acr-16 nicotinic receptor expression (p > 0.10) but increased gab-1 expression relative to controls (p < 0.01). In contrast, zygote-exposed and zygote- plus larval-exposed worms showed a similar increase in spontaneous behavior on plain plates (p < 0.001 and p = 0.001, respectively) but control levels of responding when tested on nicotine (p > 0.90 for each). However, expression of acr-16 and gab-1 was downregulated in zygote-exposed (p < 0.01 and p < 0.05, respectively) and significantly upregulated in the zygote- plus larval-exposed worms (p < 0.000 for each); most surprising was the over five-fold increase in gab-1 expression. These results suggest that spontaneous motor behavior and receptor expression are differentially modulated by nicotine exposure during larval development and/or zygote formation. As well, these findings demonstrate that C. elegans, as a model system, is also sensitive to nicotine exposure during early development and provides the basis for future research to uncover specific mechanisms by which early nicotine exposure modifies neuronal signaling and alters behavior.