Prenatal nicotine exposure decreases the release of dopamine in the medial frontal cortex and induces atomoxetine-responsive neurobehavioral deficits in mice

Tursun Alkam, Takayoshi Mamiya, Nami Kimura, Aya Yoshida, Daisuke Kihara, Yuki Tsunoda, Yuki Aoyama, Masayuki Hiramatsu, Hyoung Chun Kim, Toshitaka Nabeshima

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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.

Original languageEnglish
Pages (from-to)1853-1869
Number of pages17
JournalPsychopharmacology
Volume234
Issue number12
DOIs
Publication statusPublished - 01-06-2017

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All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Alkam, T., Mamiya, T., Kimura, N., Yoshida, A., Kihara, D., Tsunoda, Y., Aoyama, Y., Hiramatsu, M., Kim, H. C., & Nabeshima, T. (2017). Prenatal nicotine exposure decreases the release of dopamine in the medial frontal cortex and induces atomoxetine-responsive neurobehavioral deficits in mice. Psychopharmacology, 234(12), 1853-1869. https://doi.org/10.1007/s00213-017-4591-z