Research ReportChronic neonatal nicotine exposure increases excitation in the young adult rat hippocampus in a sex-dependent manner

Smoking during pregnancy exposes the fetus to nicotine, resulting in nicotine-stimulated neurotransmitter release. Recent evidence suggests that the hippocampus develops differently in males and females with delayed maturation in males. We show that chronic nicotine exposure during the first postnatal week has sex-specific long-term effects. Neonatal rat pups were chronically treated with nicotine (6 mg/kg/day) (CNN) from postnatal day 1 to 7 or milk only (Controls), and hippocampal slices were prepared from Control- and CNN-treated young adults. Field excitatory postsynaptic potentials (fEPSPs) or population spikes (PSs) were recorded from the CA1 hippocampus following CA1 s. radiatum stimulation. Input/Output curves constructed from fEPSP data indicated that CNN-males, but not females, had significantly increased excitatory responses compared to Controls (p < 0.05, n = 10 Con, n = 11 CNN). Long-term potentiation (LTP) was not significantly changed by CNN. In the presence of bicuculline, which blocks inhibitory GABAA receptors, an epileptiform burst consisting of a series of PSs was evoked. The amplitude of the first PS was significantly larger in CNN-males and females compared to Controls (males: p < 0.01, n = 8 Con, n = 8 CNN; females: p < 0.05, n = 9 Con, n = 7 CNN). Only CNN-males also had significantly larger second PSs (p < 0.05, n = 8 con, n = 8 CNN). Epileptiform activity evoked by zero Mg2 + incubation did not differ in amplitude or duration of bursts in CNN-males or females compared to Controls. These data indicate that neonatal nicotine exposure has long lasting effects and results in increased excitation within the CA1 hippocampus in adulthood, with males showing increased sensitivity to nicotine's effects.

► Chronic neonatal nicotine treatment leads to long-term changes in hippocampal field potentials. ► Both male and female rats exhibit changes in field potential responses. ► Long-term effects are less pronounced in adult females than in males. ► Young adult males show increased excitation following neonatal nicotine.