Nicotine ameliorates cognitive deficits induced by maternal LPS exposure: A study in rats

Abstract

Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin) at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg) at one of three neurodevelopmental time periods [gestation days (GD) 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND) 60] and included: prepulse inhibition (PPI), latent inhibition (LI) and delayed non-matching to sample (DNMTS). Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously) were administered, and animals were re-tested in the same tasks (PND 110). Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11) resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI) and selective (LI) improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI) and induced a global enhancement of sensorimotor gating (PPI).

Nicotine self‐administration reverses cognitive deficits in a rat model for schizophrenia

“…The data obtained in this study are consistent with our previous research (Waterhouse et al ) and others (Zuckerman & Weiner ). Animals prenatally exposed to MIA showed diminished LI.…”

“…In a previous study, we showed that the cognitive deficits induced by MIA were ameliorated after repeated experimenter‐administered NIC (Waterhouse et al ). The findings of the present study extend this to self‐administered NIC.…”

“…Pregnant female rats were administered s.c. injections once daily on two consecutive days with either LPS (0.5 mg/kg) or SAL on GD 10/11 (Waterhouse et al ). The subjects of this study were male offspring born to these dams.…”

“…Recently, we showed that maternal exposure to LPS [0.5 mg/kg, subcutaneous (s.c.)] at gestation days (GD) 10/11 (but not on GD 15/16 or GD 18/19) resulted in significant deficits in prepulse inhibition, latent inhibition (LI) and working memory (WM) [delayed non‐matching to sample (DNMTS)]. Further, some of these deficits were ameliorated by repeated experimenter‐administered NIC (0.6 mg/kg/day, s.c.) (Waterhouse et al ). This supports the hypothesis that schizophrenic patient might smoke to alleviate cognitive deficits.…”

A RATional choice for translational research?

“…The team tested the hypothesis that a high incidence of smoking in schizophrenics might be due to the putative cognitive-enhancing effects of nicotine. In support of this effect, the authors found that global cognitive deficits induced by early LPS exposure were at least in part reversed by nicotine treatment in the offspring (Waterhouse et al, 2016). …”