TY - JOUR T1 - 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 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1020 LP - 1026 DO - 10.1124/jpet.104.068692 VL - 310 IS - 3 AU - Feng Chen AU - Andrew J. Lawrence Y1 - 2004/09/01 UR - http://jpet.aspetjournals.org/content/310/3/1020.abstract N2 - 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 (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 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 labeled by [125I]FK33,824 (d-Ala2,N-Me-Phe4,Met(O)5-ol enkephalin) and the coupling between receptors and G proteins determined by agonist-stimulated guanosine 5′-O -(3-[35S]thio)triphosphate ([35S]GTPγS) 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 [125I]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 μ-opioid receptors to G proteins was determined by an increase of [35S]GTPγS binding induced by stimulation with the μ-opioid receptor agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (10 μM). 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 μ-opioid receptors to G proteins in the amygdala suggests that opioid function within the amygdala may be modulated by antidepressants. The American Society for Pharmacology and Experimental Therapeutics ER -