Chronic intrathecal morphine administration produces homologous mu receptor/G-protein desensitization specifically in spinal cord

• Published in: Brain research 2001-03, Vol.895 (1), p.1-8
• Main Authors: Maher, Catherine E, Eisenach, James C, Pan, Hui-Lin, Xiao, Ruoyu, Childers, Steven R
• Format: Article
• Language: English
• Subjects: Analgesics; Analgesics, Opioid - pharmacology; Animals; Binding Sites - drug effects; Binding Sites - physiology; Biological and medical sciences; Drug Administration Schedule; Drug Tolerance - physiology; GTP-Binding Proteins - agonists; GTP-Binding Proteins - metabolism; Guanosine Triphosphate - pharmacokinetics; Injections, Spinal; Male; Medical sciences; Morphine - pharmacology; Neuropharmacology; Pain - drug therapy; Pain - metabolism; Pain - physiopathology; Pain Threshold - drug effects; Pain Threshold - physiology; Pharmacology. Drug treatments; Posterior Horn Cells - cytology; Posterior Horn Cells - drug effects; Posterior Horn Cells - metabolism; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - metabolism; Sulfur Radioisotopes - pharmacokinetics
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)03093-6

Previous studies have shown that chronic i.v. treatment with morphine or heroin decreased mu opioid receptor activation of G-proteins in specific brain regions. The present study examined the effect of intrathecal (i.t.) morphine administration on receptor/G-protein coupling in the spinal cord. In spinal cord membranes, [ 35S]GTPγS binding was stimulated by agonists of several G-protein-coupled receptors, including mu opioid (DAMGO), delta opioid (DPDPE), GABA B (baclofen), cannabinoid CB 1 (WIN 55,212-2), muscarinic cholinergic (carbachol) and adenosine A 1 (PIA). [ 35S]GTPγS autoradiography revealed that most of this agonist activation of G-proteins was localized to laminae I and II of dorsal horn. To determine the effects of chronic morphine on these receptor activities, rats were treated for 7 days with 0.11 mg/kg/day i.t. morphine, and receptor activation of G-proteins was determined by [ 35S]GTPγS autoradiography of brain and spinal cord. In spinal cord sections, chronic morphine treatment decreased DAMGO-stimulated [ 35S]GTPγS binding in laminae I and II at all levels of spinal cord examined. There were no effects of morphine treatment on [ 35S]GTPγS stimulation in spinal cord by other receptor systems examined (Adenosine A 1 and GABA B), and no significant effects of chronic i.t. morphine treatment were observed in brain sections. These data show that homologous desensitization of mu receptor/G-protein coupling occurs specifically in spinal cord following chronic morphine administration.