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Psychopharmacology (Berl) ; 234(12): 1853-1869, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28332006

ABSTRACT

Increased risk of attention-deficit/hyperactivity disorder (AD/HD) is partly associated with the early developmental exposure to nicotine in tobacco smoke. Emerging reports link tobacco smoke exposure or prenatal nicotine exposure (PNE) with AD/HD-like behaviors in rodent models. We have previously reported that PNE induces cognitive behavioral deficits in offspring and decreases the contents of dopamine (DA) and its turnover in the prefrontal cortex (PFC) of offspring It is well known that the dysfunction of DAergic system in the brain is one of the core factors in the pathophysiology of AD/HD. Therefore, we examined whether the effects of PNE on the DAergic system underlie the AD/HD-related behavioral changes in mouse offspring. PNE reduced the release of DA in the medial PFC (mPFC) in mouse offspring. PNE reduced the number of tyrosine hydroxylase (TH)-positive varicosities in the mPFC and in the core as well as the shell of nucleus accumbens, but not in the striatum. PNE also induced behavioral deficits in cliff avoidance, object-based attention, and sensorimotor gating in offspring. These behavioral deficits were attenuated by acute treatment with atomoxetine (3 mg/kg, s.c.) or partially attenuated by acute treatment with MPH (1 mg/kg, s.c.). Taken together, our findings support the notion that PNE induces neurobehavioral abnormalities in mouse offspring by disrupting the DAergic system and improve our understanding about the incidence of AD/HD in children whose mothers were exposed to nicotine during their pregnancy.


Subject(s)
Atomoxetine Hydrochloride/toxicity , Attention Deficit Disorder with Hyperactivity/chemically induced , Dopamine/metabolism , Nicotine/toxicity , Prefrontal Cortex/metabolism , Prenatal Exposure Delayed Effects/chemically induced , Adrenergic Uptake Inhibitors/toxicity , Animals , Attention Deficit Disorder with Hyperactivity/metabolism , Attention Deficit Disorder with Hyperactivity/psychology , Cognition Disorders/chemically induced , Cognition Disorders/metabolism , Cognition Disorders/psychology , Female , Male , Mice , Mice, Inbred C57BL , Prefrontal Cortex/drug effects , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/psychology
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