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

We have previously documented that chronic alcohol consumption or alcohol withdrawal affects mu-opioid receptor density and receptor-mediated G protein coupling in Fawn-Hooded (FH) rat brain, especially in mesolimbic regions. FH rats demonstrate comorbid depression and high voluntary alcohol consumption; treatment with standard antidepressants improves both facets of this phenotype. Accordingly, we sought to examine whether mu-opioid receptor binding and the receptor-mediated functional coupling to G protein is affected by this drug treatment. Using quantitative autoradiography, binding of mu-opioid receptors labeled by [I-125] FK33,824 (D-Ala(2),N-Me-Phe(4), Met(O)(5)-ol enkephalin) and the coupling between receptors and G proteins determined by agonist-stimulated guanosine 5'-O-(3-[S-35] thio) triphosphate ([S-35] GTPgammaS) binding was mapped throughout brain sections of FH rats after 10-day treatment with vehicle, desipramine, or sertraline. Both desipramine and sertraline produced significant decreases of [I-125] FK33,824 binding in many brain regions; 13 of 20 measured regions for desipramine and 16 of 20 measured regions for sertraline. The coupling efficiency of mu-opioid receptors to G proteins was determined by an increase of [S-35] GTPgammaS binding induced by stimulation with the mu-opioid receptor agonist [D-Ala(2),N-Me-Phe(4), Gly(5)-ol]-enkephalin (10 muM). In contrast to the receptor binding profile, functional coupling of receptors to G proteins was only significantly reduced in the amygdala, whereas it remained unchanged in other regions compared with control. The present findings suggest that antidepressants regulate opioid systems; however, this occurs differentially, and region-specific alteration of functional coupling of mu-opioid receptors to G proteins in the amygdala suggests that opioid function within the amygdala may be modulated by antidepressants.