Prenatal IV nicotine exposure produces a sex difference in sensorimotor gating of the auditory startle reflex in adult rats

Abstract

Maternal smoking during pregnancy is associated with auditory processing deficits in children; these effects have been confirmed with animal models of continuous high-dose prenatal nicotine exposure. The present experiments utilized a novel, low-dose, intermittent, intravenous (IV) gestational nicotine exposure model to investigate potential deficits on the preattentive process of sensorimotor gating, as indexed by prepulse inhibition (PPI), in preweanling and adult rat offspring. Pregnant dams received bolus IV injections of nicotine (0.05 mg/kg/injection) 3x/day on gestational days 8–21. Auditory and tactile stimulus modalities were probed with tone and air puff prepulse stimuli, respectively. These prepulse stimuli preceded a 100 dB(A) startle tone by six different interstimulus intervals (ISIs; 0, 8, 40, 80, 120, 4000 ms) to define a curve of response inhibition. The magnitude of PPI increased with age, from 59 to 81% inhibition. Preweanlings (PND 14 and 18) and adults (PND 75) gestationally exposed to nicotine exhibited altered startle responding relative to controls, but the nature of the deficit became more localized at later ages. The entire curve of response inhibition in preweanlings exposed to prenatal nicotine (PND 14) was shifted up relative to controls, and notably, did not interact with prepulse stimulus modality, suggesting a generalized increased sensorimotor responsiveness as a function of prenatal nicotine. At PND 18, a shift in the response curve across all ISIs was again noted, but varied as a function of prepulse stimulus modality; the increased sensorimotor responsiveness was specific to the auditory, but not tactile, sensory modality. In adulthood, male and females animals prenatally exposed to nicotine were differentially sensitive to modulation by the ISIs, relative to control male and female animals. Specifically, despite robust PPI, adult females exposed to gestational nicotine were relatively insensitive to changes in ISI from 8–120 ms; in contrast, the robust PPI of nicotine-exposed males demonstrated a clear focal point of inhibition at 40 ms. These findings indicate that a low, daily dosing of IV prenatal nicotine produces long-lasting alterations in auditory PPI. An important implication of this research is that “chipping” with smoked-tobacco products during pregnancy may produce enduring changes in sensorimotor processing.

IV prenatal nicotine exposure increases the reinforcing efficacy of methamphetamine in adult rat offspring

“…These data are consistent with previous results from our laboratory, which indicate enduring behavioral and/or neurophysiological consequences of IV PN exposure (Harrod et al, 2012, 2011; Lacy et al, 2012, 2011; Morgan et al, 2013). Furthermore, these data support a small, but growing literature showing that PN exposure alters motivated behavior in offspring; particularly in regard to drug self-administration (Buka et al, 2003; Franke et al, 2008; Kandel et al, 1994; Levin et al, 2006; Weissman et al, 1999).…”

“…Overall, less nicotine is needed to produce behavioral alterations in offspring, relative to other exposure models. The intentional administration of low overall concentrations of daily nicotine allows the experimenter to observe potential neurodevelopmental/neurobehavioral alterations in offspring without producing differences in litter composition, low birth weight, or any of the behavioral milestones tested, relative to PS controls (Harrod et al, 2012, 2011; Lacy et al, 2012, 2011; Morgan et al, 2013). Practically, this issue is important because it suggests that the modulation of METH reinforcement in PN-exposed offspring in the present study is due to PN-mediated alterations of neural development, rather than nicotine-induced changes in birth weight, and hence, growth anomalies.…”

Intravenous Prenatal Nicotine Exposure Alters METH-Induced Hyperactivity, Conditioned Hyperactivity, and BDNF in Adult Rat Offspring

“…Our laboratory uses a model of intravenous (IV) PN exposure in rats to mimic the pharmacokinetic profile of nicotine absorption with tobacco smoke inhalation [20,21]. Several studies from our laboratory have shown that 3×/day IV nicotine administration produces significant and long-lasting neurobehavioral alterations in exposed offspring [17,21,22].…”

“…Several studies from our laboratory have shown that 3×/day IV nicotine administration produces significant and long-lasting neurobehavioral alterations in exposed offspring [17,21,22]. In the present study, we used adult male and female offspring exposed to IV PN or prenatal saline (PS) and assessed methamphetamine (METH)-induced hyperactivity and METH-induced sensitization.…”

Intravenous prenatal nicotine exposure increases orexin expression in the lateral hypothalamus and orexin innervation of the ventral tegmental area in adult male rats

“…The present experiments utilized a low-dose IV PN exposure method that has been shown to alter the expression of brain-derived neurotrophic factor in offspring (Harrod et al, 2011), and to produce alterations in various behavioral assays including prepulse inhibition of the acoustic startle response (Lacy et al, 2011), sucrose-maintained responding (Lacy et al, 2012), and methamphetamine self-administration (Harrod et al, 2012). We determined if PN exposure altered the expression of orexin in the LH and in its projections to the VTA using immunohistochemical techniques in tissue from adult offspring (~130 days) that were prenatally exposed to nicotine or saline.…”