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

Abstract

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.

Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: Association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP

“…Indeed, voltage-sensitive dye imaging revealed significant changes in the network activity of hippocampal slices from MN mice. A similar increase in CA1 excitatory activity has also been observed in rats exposed to one week of postnatal nicotine (Damborsky et al , 2012). Interestingly, we did not observe any corresponding change in fEPSP stimulus response-curves or in paired pulse facilitation, suggesting that these changes in hippocampal physiology are not occurring solely at the SC synapse.…”

Neonatal nicotine exposure increases excitatory synaptic transmission and attenuates nicotine-stimulated GABA release in the adult rat hippocampus

“…Here, we show that chronic neonatal nicotine exposure disrupts the excitatory/inhibitory balance by persistently increasing AMPAR-mediated excitation without altering inhibitory activity resulting in the overall increase in excitation as previously reported within the adult male hippocampus (Damborsky et al, 2012). Furthermore, chronic neonatal nicotine treatment attenuates nicotine-induced increases in presynaptic GABA release without altering nicotine-induced increases in glutamate release in adults.…”

“…Thus, there was little or no change in TTX-sensitive or TTX-insensitive GABA release. Together, these data suggest that the increase in overall excitation observed in the hippocampus of adult males following chronic neonatal nicotine treatment (Damborsky et al, 2012) is the result of increased glutamatergic signaling rather than a decrease in inhibitory signaling.…”

“…We have previously demonstrated increased dendritic excitation, as measured by field excitatory postsynaptic potentials (EPSPs), in the CA1 region of chronic neonatally nicotine-treated adult males compared to controls (Damborsky et al, 2012). Here, we expand upon those findings by showing that this increase in excitation is accompanied by increases in glutamatergic signaling through AMPARs in whole-cell voltage clamp recordings from CA1 pyramidal neurons.…”

“…Previously, we have shown that chronic neonatal nicotine exposure during a time period equivalent to the third trimester of human brain development (Winzer-Serhan, 2008) results in an overall increase in field excitatory postsynaptic potential (EPSP) responses within the adult male rat hippocampus (Damborsky et al, 2012). Based on these data, as well as other studies showing endogenous nicotinic cholinergic signaling is a critical component of excitatory but not inhibitory synapse formation in the hippocampus (Lozada et al, 2012a; Lozada et al, 2012b), we hypothesized that the increase in excitation in the adult hippocampus following chronic neonatal nicotine exposure is due to an increase in glutamatergic α-amino-3-hydroxy-5-methyl-4-izoxazolepropionic acid receptor (AMPAR) signaling rather than a decrease in GABAergic signaling.…”