Studies on the mechanism of antidepressants using clonal cell lines.

Research Project

Project/Area Number	61570529
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Psychiatric science
Research Institution	Saitama Medical School
Principal Investigator	HIGUCHI Teruhiko Saitama Medical School, Lecturer, 医学部, 講師 (90105883)
Co-Investigator(Kenkyū-buntansha)	EBISAWA Takashi Saitama Medical School, instructor, 医学部, 助手 (00201369) WATANABE Yoshifumi Saitama Medical School, instructor, 医学部, 助手 (90182964) 五十嵐良雄埼玉医科大学, 医学部, 助手 (20118623) 山崎潤埼玉医科大学, 医学部, 助手 (60182482)
Project Period (FY)	1986 – 1987
Project Status	Completed (Fiscal Year 1987)
Budget Amount *help	¥2,200,000 (Direct Cost: ¥2,200,000) Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000) Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywords	C6 glioma cells / <beta>-adrenoceptor / cyclic AMP / cyclic AMP / パロキセチン結合 / 再とり込み機構 / 神経系腫瘍細胞 / PC-12細胞 / 【C_6】細胞 / チロシン水酸化酵素活性 / 【β_3】レセプター
Research Abstract	The direct effects of chronic treatment with the anti-depressants on the number of <bet>-adrenoceptors and the accumulation of cyclic-AMP stimulated with isoproterenol were studied on C6 intact cultured cells. The cells were treated chronically for 5 days with 10^<-5> M decipramine (DMI), imipramine (IMI) or mianserin(MIA). Binding studies were performed with the radioligand ^3H-CGP-12177. These treatment did not induce the decrease in the number of <bet>-adrenoceptors nor the change of affinity. On the other hand, chronic exposure (4 days) to DMI or MIA led to a decrease in isoproterenol-induced accumulation of cyclic AMP in a dose dependent manner (10^<-7> -10^<-5> M). When the cells were cultured with haloperidol, the decrease in isoproterenol-induced accumulation of cyclic AMP was found only in the concentration of 10^<-5> M and 5x10^<-6> M. These result suggest that antidepressants (DMI and MIA) directly act on the secondmessenger system without any change of <bet>-adrenoceptors when these drugs were administered chronically. In addition, the concentration of 10^<-6>-10^<-7> M of antidepressants should be used for these kind of experiments because the change of the response of cyclic AMP with 10^<-5>-10^<-6> M was found to be not specific for antidepressants.