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
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 <
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.