κ-opioid agonist stimulated regional distribution of [ 35S]GTPγs binding in butorphanol continuously infused rat

• Published in: Brain research bulletin 2000-05, Vol.52 (1), p.17-20
• Main Authors: Park, Y, Jang, C.-G, Ho, I.K, Ko, K.H
• Format: Article
• Language: English
• Subjects: Analgesics; Autoradiography; Biological and medical sciences; Butorphanol; GTPγS binding; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; κ-opioid receptor
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/S0361-9230(99)00274-9

Butorphanol is a mixed agonist/antagonist opioid analgesic agent, which exerts its effects mainly by interaction with the κ-opioid receptor. Opioid receptors are coupled to G proteins of G i/G o family, and recently a decrease in μ-opioid activation of G proteins has been reported in specific brainstem nuclei after chronic morphine administration. The influence of centrally administered butorphanol on agonist-stimulated G protein coupling was examined in the rat brain, using in situ guanylyl-5′-O-(γ-[ 35S]thio)-triphosphate (GTPγS) binding autoradiography. Rats were treated with butorphanol (26 nmol/μl/h) by intracerebroventricular infusion via osmotic minipumps for 3 days. The distribution of [ 35S]GTPγS binding in the brain 7 h after the termination of butorphanol infusion was measured in the presence or absence of the selective κ-opioid agonist, U-50,488. This agonist significantly increased [ 35S]GTPγS binding in the parietal cortex, caudate putamen, thalamus, and central gray of control rats, but not in those regions of the butorphanol-infused animals. These results suggest that chronic administration of butorphanol developed tolerance and abolished U-50,488 activation of G proteins in these brain areas.