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Chronic imipramine treatment downregulates IR1-imidazoline receptors in rat brainstem.

Authors :
Zhu H
Halaris A
Piletz JE
Source :
Life sciences [Life Sci] 1997; Vol. 61 (19), pp. 1973-83.
Publication Year :
1997

Abstract

One subtype of imidazoline receptors (IR1) is similar to alpha 2-adrenoceptors (alpha 2 AR) based on their high affinity for clonidine and related imidazoline compounds. On the other hand, IR1 possess low affinity for norepinephrine (NE) and other catecholamines. Imidazoline receptors have also been found to be over-expressed in plasma membranes from platelets and brain tissues of depressed patients. Over-expression of IR1 in platelet membranes of depressed patients became normalized after various antidepressant treatment to the patients. Herein, the prototypic antidepressant, imipramine (IMI), has been studied in regard to its treatment effects on [125I]p-iodoclonidine binding to both alpha 2 AR and IR1 in rat brainstem membranes. No effects of chronic IMI treatment were found on brainstem alpha 2 AR binding sites (Bmax and/or KD parameters unchanged) after 25 days of daily injections (i.p. IMI 20 mg/kg/day). However, IMI induced a decrease in the density (Bmax measured under NE mask) of brainstem IR1 sites, with no change in KD. Downregulation of IR1 sites was dose-dependent (minimal effective dose of i.p. IMI was 10 mg/kg/day) and time-dependent (> 16 days of treatment). These results implicate brainstem IR1 in the chronic effects of antidepressants.

Details

Language :
English
ISSN :
0024-3205
Volume :
61
Issue :
19
Database :
MEDLINE
Journal :
Life sciences
Publication Type :
Academic Journal
Accession number :
9364202
Full Text :
https://doi.org/10.1016/s0024-3205(97)00837-0