TY - JOUR
T1 - Involvement of nicotinic acetylcholine receptors in behavioral abnormalities and psychological dependence in schizophrenia-like model mice
AU - Noda, Yukihiro
AU - Uchida, Mizuki
AU - Mouri, Akihiro
AU - Yamada, Shokuro
AU - Goto, Sakika
AU - Kitagaki, Shinji
AU - Mamiya, Takayoshi
AU - Kushima, Itaru
AU - Arioka, Yuko
AU - Ozaki, Norio
AU - Yoshimi, Akira
N1 - Funding Information:
This study was supported by Grants-in-Aid for Scientific Research C [grant number 24590219 (Y.N.), 26460240 (Y.N.), 16K08421 (Y.N.), 17K10325 (Y.N.)], the private University Research Project from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Y.N.), AMED under Grant Number JP18dm0107087 (N.O.), JP18dm0207005 (N.O.), JP20dm0207075 (Y.N.), JP19dk0307075 (N.O.), & JP19dk0307081 (N.O.), the Adaptable and Seamless Technology Transfer Program Through Target-driven R&D, Japan Science and Technology Agency (grant number AS251Z03018) (Y.N.), Meijo University Research Institute grant (Y.N.), and the SRF (Y.N.). Participated in research design: Noda, Mouri, Kushima, Arioka, Ozaki, Conducted experiments: Noda, Uchida, Mouri, Yamada, Goto, Kitagaki, Mamiya, Kushima, Yoshimi, Performed data analysis: Noda, Uchida, Yamada, Goto, Arioka, Ozaki, Yoshimi, Wrote or contributed to the writing of the manuscript: Noda, Mouri, Goto, Yoshimi. We would like to thank Mr. Koki Soeda, Ms. Ayumi Ishihara, and all staff members of Faculty of Pharmacy, Meijo University that were involved in this study.
Funding Information:
This study was supported by Grants-in-Aid for Scientific Research C [grant number 24590219 (Y.N.) , 26460240 (Y.N.) , 16K08421 (Y.N.) , 17K10325 (Y.N.) ], the private University Research Project from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Y.N.), AMED under Grant Number JP18dm0107087 (N.O.), JP18dm0207005 (N.O.) , JP20dm0207075 (Y.N.) , JP19dk0307075 (N.O.) , & JP19dk0307081 (N.O.) , the Adaptable and Seamless Technology Transfer Program Through Target-driven R&D, Japan Science and Technology Agency (grant number AS251Z03018 ) (Y.N.), Meijo University Research Institute grant (Y.N.) , and the SRF (Y.N.) .
Publisher Copyright:
© 2020 Elsevier B.V. and ECNP
PY - 2020/12
Y1 - 2020/12
N2 - The smoking incentive in patients with schizophrenia (SCZ) depends on stimulation of nicotinic acetylcholine receptors (nAChRs) in the central nervous system. To detect potential predictor genes for nicotine responses in SCZ, we explored common factor using research data in human and animal samples. In lymphoblastoid cell lines from SCZ, the mRNA expression level of α7 nAChR subunit was decreased. In SCZ-like model mice of phencyclidine (PCP; 10 mg/kg/day, subcutaneously for 14 days)-administered mice, the mRNA expression level of α7 nAChR subunit and protein expression level of α7 or α4 nAChR subunit were significantly decreased in the prefrontal cortex during PCP withdrawal. Protein, but not mRNA, expression levels of α7, α4, and β2 nAChR subunits were significantly increased in the nucleus accumbens. Acute (-)-nicotine [(-)-NIC: 0.3 mg/kg, s.c.] treatment attenuated impairments of social behaviors and visual recognition memory. These effects of (-)-NIC were completely blocked by both methyllycaconitine, a selective α7 nAChR antagonist, and dihydro-β-erythroidine (DHβE), a selective α4β2 nAChR antagonist. (-)-NIC did not induce conditioned place preference, but enhanced sensitivity to methamphetamine-induced hyperactivity. These findings suggest that α7 nAChR is associated with development of disease and is implicated in the therapeutic effect of nicotine in SCZ. The smoking incentive in SCZ might be attributed to treat their own symptoms, rather than a result of (-)-NIC dependence, by stimulating α7 and/or α4β2 nAChRs.
AB - The smoking incentive in patients with schizophrenia (SCZ) depends on stimulation of nicotinic acetylcholine receptors (nAChRs) in the central nervous system. To detect potential predictor genes for nicotine responses in SCZ, we explored common factor using research data in human and animal samples. In lymphoblastoid cell lines from SCZ, the mRNA expression level of α7 nAChR subunit was decreased. In SCZ-like model mice of phencyclidine (PCP; 10 mg/kg/day, subcutaneously for 14 days)-administered mice, the mRNA expression level of α7 nAChR subunit and protein expression level of α7 or α4 nAChR subunit were significantly decreased in the prefrontal cortex during PCP withdrawal. Protein, but not mRNA, expression levels of α7, α4, and β2 nAChR subunits were significantly increased in the nucleus accumbens. Acute (-)-nicotine [(-)-NIC: 0.3 mg/kg, s.c.] treatment attenuated impairments of social behaviors and visual recognition memory. These effects of (-)-NIC were completely blocked by both methyllycaconitine, a selective α7 nAChR antagonist, and dihydro-β-erythroidine (DHβE), a selective α4β2 nAChR antagonist. (-)-NIC did not induce conditioned place preference, but enhanced sensitivity to methamphetamine-induced hyperactivity. These findings suggest that α7 nAChR is associated with development of disease and is implicated in the therapeutic effect of nicotine in SCZ. The smoking incentive in SCZ might be attributed to treat their own symptoms, rather than a result of (-)-NIC dependence, by stimulating α7 and/or α4β2 nAChRs.
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U2 - 10.1016/j.euroneuro.2020.10.001
DO - 10.1016/j.euroneuro.2020.10.001
M3 - Article
C2 - 33109433
AN - SCOPUS:85094582198
VL - 41
SP - 92
EP - 105
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
SN - 0924-977X
ER -