Multiple nicotinic acetylcholine receptor subtypes regulate social or cognitive behaviors in mice repeatedly administered phencyclidine
Multiple nicotinic acetylcholine receptor subtypes regulate social or cognitive behaviors in mice repeatedly administered phencyclidine
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多种烟碱乙酰胆碱受体亚型调节重复服用苯环己哌啶的小鼠的社会或认知行为
DOI：
10.1016/j.bbr.2021.113284
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发表时间：
2021
影响因子：
2.7
通讯作者：
Mouri Akihiro
中科院分区：
文献类型：
--
作者：
Noda Yukihiro;Soeda Koki;Uchida Mizuki;Goto Sakika;Ito Takahiro;Kitagaki Shinji;Mamiya Takayoshi;Yoshimi Akira;Ozaki Norio;Mouri Akihiro
精神分裂症（SCZ）患者的习惯性吸烟被认为可以通过刺激中枢神经系统中的烟碱乙酰胆碱受体（nAChR）来改善其自身的精神病或对（-）-尼古丁（[-]-NIC）产生心理依赖。在本研究中，我们使用反复给予苯环己哌啶（PCP：10 mg/kg/天，皮下注射14天）的小鼠作为SCZ样模型小鼠，研究了习惯性吸烟是否是为了获得治疗效果或心理依赖以及哪些nAChR亚基与之相关。反复注射五氯苯酚的小鼠表现出社交或认知行为受损；前额皮质 (PFC) 中 α7 和/或 α4 nAChR 亚基的表达减少；伏隔核 (NAc) 中 α7、α4 和 β2 nAChR 亚基的表达增加。这些变化通过重复施用(-)-NIC而减弱。选择性 α7 nAChR 拮抗剂和选择性 α4β2 nAChR 拮抗剂可防止对行为障碍的减弱作用。在单独使用非有效剂量或弱有效剂量时，(-)-NIC (0.03 mg/kg) 和利培酮 (0.03 mg/kg) 的共同给药对 PCP 给药小鼠的行为损伤显示出协同作用。重复 (-)-NIC 给药不会影响条件性位置偏好的表现，但在 PCP 给药的小鼠中显示出对 (-)-NIC 的行为敏感性。重复给予 (-)-NIC 并不影响条件性位置偏爱的表现，但在 PCP 给药的小鼠中，它表现出对 (-)-NIC 的行为敏感性以及对氟哌啶醇诱导的僵直症的减弱作用。我们的研究结果表明，SCZ 中习惯性吸烟可能有助于获得治疗并减少 (-)-NIC 激活 α7 和 α4β2 nAChR 介导的副作用。
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.
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影响因子：
3.7
作者：
Thomsen MS;El-Sayed M;Mikkelsen JD
通讯作者：
Mikkelsen JD
尼古丁从大鼠海马突触体释放[3H]-去甲肾上腺素：纹状体[3H]-多巴胺释放中不同烟碱受体亚型的介导
影响因子：
7.3
作者：
P. Clarke;M. Reuben
通讯作者：
M. Reuben
影响因子：
16.2
作者：
Gu, Shenyan;Matta, Jose A.;Bredt, David S.
通讯作者：
Bredt, David S.
影响因子：
2.5
作者：
Kleijn, J.;Folgering, J. H. A.;Westerink, B. H. C.
通讯作者：
Westerink, B. H. C.
影响因子：
7.3
作者：
MADDOX, VH;GODEFROI, EF;PARCELL, RF
通讯作者：
PARCELL, RF