Prenatal nicotine exposure decreases the release of dopamine in the medial frontal cortex and induces atomoxetine-responsive neurobehavioral deficits in mice.
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.
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.|Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA.
Tursun
T
Alkam
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.|Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
Takayoshi
T
Mamiya
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Nami
N
Kimura
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Aya
A
Yoshida
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Daisuke
D
Kihara
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Yuki
Y
Tsunoda
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Yuki
Y
Aoyama
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.|Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
Masayuki
M
Hiramatsu
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, South Korea.
Hyoung-Chun
HC
Kim
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan. tnabeshi@ccalumni.meijo-u.ac.jp.|Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan. tnabeshi@ccalumni.meijo-u.ac.jp.|Advanced Diagnostic System Research Laboratory, Graduate School of Health Sciences, Fujita Health University, Toyoake, Aichi, 470-1192, Japan. tnabeshi@ccalumni.meijo-u.ac.jp.|Aino University, Ibaraki, Japan. tnabeshi@ccalumni.meijo-u.ac.jp.
Toshitaka
T
Nabeshima
D018759:Adrenergic Uptake Inhibitors / Q000633:toxicity; D000818:Animals; D000069445:Atomoxetine Hydrochloride / Q000633:toxicity*; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000523:psychology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000633:toxicity*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology
D018759:Adrenergic Uptake Inhibitors; D000069445:Atomoxetine Hydrochloride; D009538:Nicotine; D004298:Dopamine
Atomoxetine; Cliff avoidance; Dopamine; Object-based attention; Prenatal nicotine exposure