Chronic imipramine treatment downregulates IR 1-imidazoline receptors in rat brainstem

Abstract

One subtype of imidazoline receptors (IR 1) is similar to α 2-adrenoceptors (α 2AR) based on their high affinity for clonidine and related imidazoline compounds. On the other hand, IR 1 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 IR 1 in platelet membranes of depressed patients became normalized after various antidepressant treatments 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 α 2AR and IR 1 in rat brainstem membranes. No effects of chronic IMI treatment were found on brainstem α 2AR binding sites (B max and/or K D parameters unchanged) after 25 days of daily injections (i.p. IMI 20 mg/kg/day). However, IMI induced a decrease in the density (B max measured under NE mask) of brainstem IR 1 sites, with no change in K D. Downregulation of IR 1 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 IR 1 in the chronic effects of antidepressants.