Enhancement of the serotonin-mediated acetylcholine release by repeated desmethylimipramine treatment in the hippocampus of freely moving rats.
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 microM) perfusion enhanced significantly the ACh release. However, 5-HT in acutely DMI-treated rats enhanced significantly the ACh release only at 10 microM. 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.
Fujii
T
T
Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
Ohba
S
S
Nakai
K
K
Fujimoto
K
K
Suzuki
T
T
Kawashima
K
K
D000109:Acetylcholine / Q000378:metabolism*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D004357:Drug Synergism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D010276:Parasympatholytics / Q000494:pharmacology; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D012886:Skull / Q000601:surgery; D013997:Time Factors; D014665:Vasodilator Agents / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D010276:Parasympatholytics; D014665:Vasodilator Agents; D012701:Serotonin; D001285:Atropine; D000109:Acetylcholine; D003891:Desipramine