Takeshi Fujii, Shigeru Ohba, Katsuhiko Nakai, Kazuko Fujimoto, Takeshi
Suzuki and Koichiro Kawashima (*)
Department of Pharmacology, Kyoritsu College of Pharmacy, 1 - 5 - 30 Shibakoen, Minato-ku, Tokyo 105 - 8512, Japan
(*) To whom correspondence should be addressed.
Abstract: 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 ÊM) perfusion enhanced significantly the ACh release. However, 5-HT in acutely DMI-treated rats enhanced significantly the ACh release only at 10 ÊM. 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.
Keywords: Acetylcholine, Desmethylimipramine, Hippocampus, Microdialysis, Serotonin (5-HT)