The influence of adolescent nicotine exposure on ethanol intake and brain gene expression

Abstract

Nicotine and alcohol are often co-abused. Adolescence is a vulnerable period for the initiation of both nicotine and alcohol use, which can lead to subsequent neurodevelopmental and behavioral alterations. It is possible that during this vulnerable period, use of one drug leads to neurobiological alterations that affect subsequent consumption of the other drug. The aim of the present study was to determine the effect of nicotine exposure during adolescence on ethanol intake, and the effect of these substances on brain gene expression. Forty-three adolescent female C57BL/6J mice were assigned to four groups. In the first phase of the experiment, adolescent mice (PND 36–41 days) were exposed to three bottles filled with water or nicotine (200 μg/ml) for 22 h a day and a single bottle of water 2 h a day for six days. In the second phase (PND 42–45 days), the 4-day Drinking-in-the-Dark paradigm consisting of access to 20% v/v ethanol or water for 2h or 4h (the last day) was overlaid during the time when the mice did not have nicotine available. Ethanol consumption (g/kg) and blood ethanol concentrations (BEC, mg %) were measured on the final day and whole brains including the cerebellum, were dissected for RNA sequencing. Differentially expressed genes (DEG) were detected with CuffDiff and gene networks were built using WGCNA. Prior nicotine exposure increased ethanol consumption and resulting BEC. Significant DEG and biological pathways found in the group exposed to both nicotine and ethanol included genes important in stress-related neuropeptide signaling, hypothalamic–pituitary–adrenal (HPA) axis activity, glutamate release, GABA signaling, and dopamine release. These results replicate our earlier findings that nicotine exposure during adolescence increases ethanol consumption and extends this work by examining gene expression differences which could mediate these behavioral effects.

Adolescent alcohol and nicotine exposure alters the adult response to alcohol use

“…The discrepancy between studies seems to be related to when in adolescence (i.e., early, mid, or late) the animals are exposed to nicotine as well as the species used (mouse versus rat). For instance, oral nicotine exposure (200 μg/mL/22 h) during early-mid adolescence (∼PND 35–44) increases binge-like ethanol consumption and BECs in mid adolescence (∼PND 45–48) in female C57BL/6J mice [ 85 , 86 ]. Oral nicotine consumption (30 μg/mL) using the DID model during late adolescence (PND 42–56) did not affect subsequent binge-like ethanol consumption in early adulthood in male C57BL/6J mice (PND 56–78) [ 87 ].…”