Multigenerational nicotine exposure affects offspring nicotine metabolism, nicotine-induced hypothermia, and basal corticosterone in a sex-dependent manner

Abstract

Parental nicotine exposure can impact phenotypes in unexposed offspring. Our laboratory recently published data showing that nicotine reward and hippocampal gene expression involved in stress pathways were perturbed in F1 offspring of male C57BL/6J mice chronically exposed to nicotine. For the current study, we aimed to further test nicotine and stress-sensitivity phenotypes that may predict vulnerability to nicotine addiction in new cohorts of F1 offspring derived from nicotine-exposed males. We tested locomotor and body temperature sensitivity to acute nicotine administration, serum concentration of nicotine and nicotine metabolites after acute nicotine dosing, and serum corticosterone levels in male and female F1 offspring of nicotine- or saline-exposed males. Paternal nicotine exposure reduced sensitivity to nicotine-induced hypothermia in males, altered nicotine metabolite concentrations in males and females, and reduced serum basal corticosterone levels in females. These findings may point to reduced susceptibility to nicotine addiction-related phenotypes as a result of parental nicotine exposure.

Keywords: Acetylcholine; Addiction; Genetic; Intergenerational inheritance; Metabolism; Stress.

Fig. 1.. Nicotine-sired males are less sensitive to nicotine-induced hypothermia

NIC-Sired males were less sensitive to acute nicotine-induced hypothermia compared to SAL-Sired males. Sample size per experimental group is shown at the top of each data bar. Error bars indicate ±SEM.*p < .05.

Fig. 2. Multigenerational nicotine exposure alters F1 nicotine metabolism

Serum nicotine concentration was higher in NIC-Sired females compared to SAL-Sired females (panel A). Serum cotinine concentration was higher in NIC-Sired animals compared to SAL-Sired animals (panel B). Serum 3’-hydroxycotinine concentration was higher in males compared to females (panel C). Serum 3’-hydroxycotinine/cotinine ratio was lower in NIC-Sired males compared to SAL-Sired males (panel D). Sample size per experimental group is shown at the bottom of each data bar. Error bars indicate ±SEM.*p < .05.

Fig. 3:. Basal serum corticosterone is lowered in nicotine-sired animals

Basal serum corticosterone concentration was lower in NIC-Sired females compared to SAL-Sired females. The difference between basal serum corticosterone did not reach significance in males. Sample size per experimental group is shown at the bottom of each data bar. Error bars indicate ±SEM.*p < .05.