Received for publication March 22, 2004.
Revised April 27, 2004.
Accepted for publication April 28, 2004.

CHRONIC ANTIDEPRESSANT TREATMENT CAUSES A SELECTIVE REDUCTION OF µ-OPIOID RECEPTOR BINDING AND FUNCTIONAL COUPLING TO G-PROTEINS IN THE AMYGDALA OF FAWN-HOODED RATS

Abstract

We have previously documented that chronic alcohol consumption or alcohol withdrawal affects µ-opioid receptor density and receptor-mediated G-protein coupling in Fawn-Hooded rat brain, especially in mesolimbic regions (Chen and Lawrence, 2000; Djouma and Lawrence, 2002). Fawn-Hooded (FH) rats demonstrate co-morbid depression and high voluntary alcohol consumption; treatment with standard antidepressants improves both facets of this phenotype. Accordingly, we sought to examine whether µ-opioid receptor binding and the receptor-mediated functional coupling to G-protein is affected by this drug treatment. Using quantitative autoradiography, binding of µ-opioid receptors labelled by [¹²⁵I]FK33,824 (D-Ala², N-Me-Phe⁴-Met(O)-ol⁵-enkephalin) and the coupling between receptors and G-proteins determined by agonist-stimulated [³⁵S]GTPS ([³⁵S]guanosine-5'-O-(3-thio)triphosphate) binding was mapped throughout brain sections of FH rats following 10 days treatment with vehicle, desipramine or sertraline. Both desipramine and sertraline produced significant decreases of [¹²⁵I]FK33,824 binding in many brain regions; 13 out of 20 measured regions for desipramine, and 16 out of 20 measured regions for sertraline. The coupling efficiency of µ-opioid receptors to G-proteins was determined by an increase of [^35S]GTPS binding induced by stimulation with the µ-opioid receptor agonist DAMGO (D-Ala², N-Me-Phe⁴-Gly-ol⁵-enkephalin; 10 µM). In contrast to the receptor binding profile, functional coupling of receptors to G-proteins was only significantly reduced in the amygdala while it remained unchanged in other regions compared to control. The present findings suggest that antidepressants regulate opioid systems, however, this occurs differentially and region-specific alteration of functional coupling of µ-opioid receptors to G proteins in the amygdala suggests that opioid function within the amygdala may be modulated by antidepressants.

Key words: amygdala, autoradiography, binding, depression, functional coupling, opioids