Apparent down-regulation of rat brain μ and κ-opioid binding sites labelled with [3H]cycloFOXY following chronic administration of the potent 5-hydroxytryptamine reuptake blocker, clomipramine

Author:

Benkelfat Chawki1,Aulakh Charanjit S1,Bykov Victor2,Rice Kenner C3,de Costa Brian R3,Rothman Richard B2

Affiliation:

1. Section on Clinical Neuropharmacology, National Institute of Mental Health

2. Unit on Receptor Studies, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20892, USA

3. Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

Abstract

Abstract This study examined the effect of chronic clomipramine administration on opioid μ- and κ-binding sites. Clomipramine (5 mg kg−1 day−1) or saline was administered to rats via osmotic minipumps for 3 days or 28 days. Lysed-P2 brain membranes were prepared and preincubated for 60 min without (control membranes) or with 1 μM of the μ-selective acylating agent, 2-(4-ethoxybenzyl)-1-diethylaminoethyl-5-isothiocyanato-benzimidazole-HCl (BIT), to deplete membranes of μ-binding sites. [3H]6-Desoxy-6β-fluoronaltrexone ([3H]cycloFOXY) was used to label μ and κ-binding sites. Weighted nonlinear least squares analysis of cycloFOXY binding surfaces permitted determination of the Kd and Bmax values of μ- and κ-binding sites in control and treated rats. Subacute (3 days) administration of rats with clomipramine had no significant effect on [3H]cycloFOXY binding. Chronic (28 days) administration of clomipramine produced a small (approximately 10%) but statistically significant decrease in the Bmax. These findings are discussed in reference to other studies that have examined the effect of chronic antidepressant administration on opioid receptors, and speculate that the endogenous opioid systems may play a role in obsessive-compulsive disorder.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference26 articles.

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