ROLE OF SPINAL MU-OPIOID RECEPTORS IN THE DEVELOPMENT OF MORPHINE-TOLERANCE AND DEPENDENCE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 231  (1) , 91-96
Abstract
The spinal cord has been shown as a primary site for the development of morphine-induced tolerance and dependence. In the current investigation, the significance of .mu. opioid receptors in the spinal cord in tolerance and dependence induced by systemically administered morphine was determined. Rats surgically implanted with intrathecal (i.t.) catheters were injected i.t. with various doses of .beta.-funaltrexamine (.beta.-FNA), a specific irreversible .mu. opioid receptor antagonist. .beta.-FNA (i.t.) dose-dependently antagonized morphine-induced analgesia (i.p.) with .apprx. 1/2 the potency of .beta.-chlornaltrexamine, a nonselective irreversible opioid receptor antagonist. Rats injected with saline i.t. 24 h before implanting morphine pellets developed a significant degree of tolerance and dependence 72 h after morphine administration. Tolerance did not develop in similarly treated animals that received i.t. injections of 4.5 nmol .beta.-FNA. Signs of naloxone-precipitated withdrawal were also significantly antagonized in all instances, except weight loss, in animals pretreated with .beta.-FNA (i.t.). Thus, i.t. injections of .beta.-FNA significantly antagonized the development of tolerance and dependence induced by systemically administered morphine. Therefore, .mu. opioid receptors within the spinal cord, and probably throughout the CNS, play a primary role in morphine-induced tolerance and dependence.