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

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. Copyright (C) 2000 Elsevier Science Inc.