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

Chen, F and Lawrence, A 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', Journal of Pharmacology and Experimental Therapeutics, vol. 310, no. 3, pp. 1020-1026.


Document type: Journal Article
Collection: Journal Articles

Title 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
Author(s) Chen, F
Lawrence, A
Year 2004
Journal name Journal of Pharmacology and Experimental Therapeutics
Volume number 310
Issue number 3
Start page 1020
End page 1026
Total pages 7
Publisher American Society for Pharmacology and Experimental Therapeutics
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 (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-Phe 4,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]GTP?S) 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]GTP?S binding induced by stimulation with the μ-opioid receptor agonist [D-Ala 2,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.
Subject Basic Pharmacology
DOI - identifier 10.1124/jpet.104.068692
ISSN 0022-3565
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