Multiple nicotinic acetylcholine receptor subtypes regulate social or cognitive behaviors in mice repeatedly administered phencyclidine

Yukihiro Noda, Koki Soeda, Mizuki Uchida, Sakika Goto, Takahiro Ito, Shinji Kitagaki, Takayoshi Mamiya, Akira Yoshimi, Norio Ozaki, Akihiro Mouri

研究成果: Article査読

抄録

Habitual smoking in patients with schizophrenia (SCZ) is considered to improve their own psychoses or to develop a vulnerability to psychological dependence on (-)-nicotine ([-]-NIC) by stimulating nicotinic acetylcholine receptors (nAChRs) in the central nervous system. In the present study, we investigated whether habitual smoking is due to get therapeutic effect or to psychological dependence and which nAChR subunits are associated with them using mice that were repeatedly administered phencyclidine (PCP: 10 mg/kg/day, s.c. for 14 days) as SCZ-like model mice. Mice that were repeatedly administered PCP showed impairments in social or cognitive behaviors; decreased expression of α7 and/or α4 nAChR subunits in the prefrontal cortex (PFC); and increased expression of α7, α4, and β2 nAChR subunits in the nucleus accumbens (NAc). These changes were attenuated by repeated administration of (-)-NIC. The attenuating effects on behavioral impairments were prevented by a selective α7 nAChR antagonist and a selective α4β2 nAChR antagonist. At non- or weak effective dose by themselves, co-administration of (-)-NIC (0.03 mg/kg) and risperidone (0.03 mg/kg) showed synergistic effects on behavioral impairments in PCP-administered mice. Repeated (-)-NIC administration did not affect the performance of conditioned place preference, while it showed behavioral sensitization to (-)-NIC in the PCP-administered mice. Repeated (-)-NIC administration did not affect the performance of conditioned place preference, while it showed behavioral sensitization to (-)-NIC and attenuating effect on haloperidol-induced catalepsy in the PCP-administered mice. Our findings suggest that habitual smoking in SCZ might be attributed to get therapeutic and reduce side effects mediated by α7 and α4β2 nAChR activation by (-)-NIC.

本文言語English
論文番号113284
ジャーナルBehavioural Brain Research
408
DOI
出版ステータスPublished - 25-06-2021

All Science Journal Classification (ASJC) codes

  • 行動神経科学

フィンガープリント

「Multiple nicotinic acetylcholine receptor subtypes regulate social or cognitive behaviors in mice repeatedly administered phencyclidine」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル