Enhancement of the serotonin-mediated acetylcholine release by repeated desmethylimipramine treatment in the hippocampus of freely moving rats

被引:6
|
作者
Fujii, T [1 ]
Ohba, S [1 ]
Nakai, K [1 ]
Fujimoto, K [1 ]
Suzuki, T [1 ]
Kawashima, K [1 ]
机构
[1] Kyoritsu Coll Pharm, Dept Pharmacol, Minato Ku, Tokyo 1058512, Japan
来源
JAPANESE JOURNAL OF PHARMACOLOGY | 1999年 / 80卷 / 04期
关键词
acetylcholine; desmethylimipramine; hippocampus; microdialysis; serotonin (5-HT);
D O I
10.1254/jjp.80.303
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A possible involvement of serotonin-mediated cholinergic activation in the antidepressant effect of desmethylimipramine (DMI) was investigated by determination of the effects of a single or repeated DMI administration on acetylcholine (ACh) release in the hippocampus using an in vivo microdialysis technique and a radioimmunoassay for ACh. Rats were administered DMI (10 mg/kg, i.p.) acutely or repeatedly for 21 days. A single or repeated DMI administration did not cause any significant effects on the basal ACh release compared with the respective controls. Atropine perfusion in the acutely DMI-treated or control rats increased the ACh release to the same degree. In repeatedly DMI-treated rats, serotonin (5-HT) (1 to 10 mu M) perfusion enhanced significantly the ACh release. However, 5-HT in acutely DMI-treated rats enhanced significantly the ACh release only at 10 mu M. 5-HT did not cause any changes in ACh release in control rats. Hippocampal 5-HT content of acutely DMI-treated rats was significantly higher than that of saline-treated control rats, while no difference was observed between the repeatedly DMI- and saline-treated rats. These findings suggest, for the first time, that DMI induced a facilitation of cholinergic neurotransmission in the rat hippocampus through the activation of 5-HT-receptor function.
引用
收藏
页码:303 / 309
页数:7
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