Environmental factors such as maternal and neonatal infection are potentially associated with the pathogenesis
of various psychiatric disorders, including schizophrenia. Polyriboinosinic-polyribocytidilic acid (polyI:C) is a synthetic
analogue of double-stranded RNA that induces strong innate immune responses. We have recently developed the mouse
model of neurodevelopmental psychiatry disorders that exhibits emotional and cognitive impairments in adulthood
following neonatal polyI:C treatment. In this study, we examined whether nicotine ameliorates emotional and cognitive
impairments in the neonatal polyI:C model because recent studies have indicated the therapeutic benefits of nicotine in
schizophrenia. Neonatal ICR mice were repeatedly injected with polyI:C (5 mg/kg, s.c.) for 5 days (postnatal days 2 to 6).
At postnatal 10 weeks, emotional functions were analyzed in open field and social interaction tests. Cognitive function
was analyzed in novel object recognition and prepulse inhibition (PPI) tests. PolyI:C-treated mice showed an increase in
anxiety-like behaviors and impairments in social behaviors, object recognition memory, and PPI, compared with the
vehicle-treated control group. Nicotine (0.15 and 0.5 mg/kg, s.c.) dose-dependently improved polyI:C-induced
impairments of emotional and cognitive behaviors, but had no effect on PPI deficit. The ameliorating effect of nicotine
was antagonized by pretreatment with dihydro-β-erythroidine or methyllycaconitine. These results suggest that nicotine
ameliorates emotional and cognitive impairments of the present polyI:C model through nicotinic acetylcholine receptors.