PreNatal nicotine exposure and maternal separation alter the nicotinic acetylcholine receptors in mice.

Abstract

Maternal cigarette smoking during pregnancy has been associated with long term cognitive dysfunction. The harmful behavioural effects of cigarette smoking have been shown to be primarily due to nicotine. While the mechanism of nicotine’s harmful actions remain unclear, studies have shown a link to the hypothalamus–pituitary–adrenal (HPA) axis. HPA axis dysfunction as a consequence of exposure to perinatal stressors such as maternal separation results in major long-term systemic and neurological disruptions and malfunction. Using a mouse model we showed that prenatal nicotine exposure (PNE) resulted in hyperlocomotivity. There are also long-term increases of the α7 nicotinic acetylcholine receptor (n-AChR) expression while the α4 n-AChR expression was decreased. Glucocorticoid receptor (GR) expression varied in the PNE groups by brain location, while no changes were found in dopamine concentration in the hippocampus or striatum. Maternally separated animals exhibited anxiety-like behaviour in the open field test. There were also significant changes in the hippocampal expression of n-AChRs, specifically decreased α4 expression and increased α7 expression of the maternally separated animals suggesting a link between HPA dysfunction and cholinergic signalling. Animals exposed to both stress and nicotine insults however show no significant difference in α7 nAChR, GR or dopamine levels when compared to the control. However, α4 nAChR expression was significantly different in the hippocampus but not the striatum of animals who experienced both insults when compared to the control. This suggests that this may be due to competitive inhibition as a result of the link between nicotine exposure in utero and HPA axis dysfunction.