Long-term clomipramine treatment upregulates forebrain acetylcholine muscarinic receptors, and reduces behavioural sensitivity to scopolamine in mice

Citation
H. Tsukagoshi et al., Long-term clomipramine treatment upregulates forebrain acetylcholine muscarinic receptors, and reduces behavioural sensitivity to scopolamine in mice, J PHARM PHA, 52(1), 2000, pp. 87-92
Citations number
19
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACY AND PHARMACOLOGY
ISSN journal
0022-3573 → ACNP
Volume
52
Issue
1
Year of publication
2000
Pages
87 - 92
Database
ISI
SICI code
0022-3573(200001)52:1<87:LCTUFA>2.0.ZU;2-7
Abstract
We have investigated the effects of long-term treatment with clomipramine, a tricyclic antidepressant, on central muscarinic acetylcholine receptors ( mAChR) in mice. Repeated clomipramine administration resulted in an increase in the forebra in receptor density value (B-max) for [H-3]quinuclidinyl benzilate, a musca rinic ligand (P < 0.05), that was dependent on dose per administration (sal ine or 5, 10, or 20 mg kg(-1) once a day for 7 days) and number of days tre ated (20 mg kg(-1) for 1, 3, 5, or 7 days). No change in apparent affinity (defined as the reciprocal of the dissociation constant) (K-D) occurred. Se ven daily treatments with clomipramine (saline or 5, 10, or 20 mg kg(-1)) r educed hyperlocomotion induced by scopolamine (0.5 mg kg(-1), s.c.) dose-de pendently, and the effect of 20 mg kg(-1) clomipramine was significant (P < 0.05). These results suggest that an upregulation of mAChR is produced by repeated clomipramine administration, and such a change is responsible for the decr eased sensitivity to the muscarinic antagonist scopolamine.