Long-term clomipramine treatment upregulates forebrain acetylcholine muscarinic receptors, and reduces behavioural sensitivity to scopolamine in mice.
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 forebrain receptor density value (Bmax) for [3H]quinuclidinyl benzilate, a muscarinic ligand (P < 0.05), that was dependent on dose per administration (saline or 5, 10, or 20 mg kg(-1) once a day for 7 days) and number of days treated (20 mg kg(-1) for 1, 3, 5, or 7 days). No change in apparent affinity (defined as the reciprocal of the dissociation constant) (KD) occurred. Seven daily treatments with clomipramine (saline or 5, 10, or 20 mg kg(-1)) reduced hyperlocomotion induced by scopolamine (0.5 mg kg(-1), s.c.) dose-dependently, 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 decreased sensitivity to the muscarinic antagonist scopolamine.
Tsukagoshi
H
H
Department of Anesthesiology and Reanimatology, Gunma University School of Medicine and Hospital, Maebashi, Japan.
Morita
T
T
Hitomi
S
S
Saito
S
S
Kadoi
Y
Y
Uchihashi
Y
Y
Kuribara
H
H
Goto
F
F
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001665:Binding Sites / Q000187:drug effects; D002997:Clomipramine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012044:Regression Analysis; D012601:Scopolamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000929:Antidepressive Agents, Tricyclic; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D012601:Scopolamine; D002997:Clomipramine