Mu-opioid receptor activation underpins clinical analgesia and is the central event in the abuse of narcotics. Continued opioid use produces tolerance to the acute effects of the drug and adaptations that lead to physical and psychological dependence. Continued mu-receptor signaling provides the engine for these adaptations, with most evidence suggesting that chronic agonist treatment produces ...

BACKGROUND A difficult problem in treating opioid addicts is the maintenance of a drug-free state because of the negative emotional symptoms associated with withdrawal, which may trigger relapse. Several lines of evidence suggest a role for the metabotropic glutamate receptor 5 in opioid addiction; however, its involvement during opioid withdrawal is not clear. METHODS Mice were treated with ...

In contrast to endogenous opioids, the highly addictive drug morphine activates the mu-opioid receptor without causing its rapid endocytosis. It has recently been reported that coapplication of low concentrations of [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) facilitates the ability of morphine to stimulate mu-opioid receptor endocytosis and prevents the development of morphine toleranc...

The purpose of this study was to evaluate the effects of the gonadal hormones on the opioid receptor protein levels of Freund's adjuvant-treated (arthritic) male and female Lewis rats. Following a paw pressure nociception assay, the midbrain and spinal cord tissues were collected for comparison of mu, delta, and kappa opioid receptor protein levels. The effects of Freund's adjuvant-induced hype...

There is increasing evidence that the signal transduction of opioid receptors is modulated by receptor-associated proteins. In the search for proteins regulating mu-opioid receptor (MOPr) endocytosis, synaptophysin was found to bind to the rat micro-opioid receptor in yeast two-hybrid assay. Coimmunoprecipitation experiments and bioluminescence resonance energy transfer assays confirmed that th...

Structural modification of salvinorin A, the active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study a nonnitrogenous neoclerodane diterpene with mu opioid receptor affinity (13) that is an agonist at mu opioid receptors. This represents the identification of a novel structural class...

Ventricular administration of the opioid dynorphin A(1-17) induces feeding in rats. Because its pharmacological characterization has not been fully identified, the present study examined whether a dose-response range of general and selective opioid antagonists as well as antisense oligodeoxynucleotide (AS ODN) opioid probes altered daytime feeding over a 4-h time course elicited by dynorphin. D...

Recently, δ opioid receptor agonists have been proposed to be attractive targets for the development of novel antidepressants. Several studies revealed that single treatment of δ opioid receptor agonists produce antidepressant-like effects in the forced swimming test, which is one of the most popular animal models for screening antidepressants. In addition, subchronic treatment with δ opioid re...

BACKGROUND Methadone is a unique µ-opioid receptor agonist. Although several researchers have insisted that the pharmacological effects of methadone are mediated through the blockade of NMDA receptor, the underlying mechanism by which methadone exerts its distinct pharmacological effects compared to those of other µ-opioid receptor agonists is still controversial. In the present study, we furth...

There is growing evidence that tonic activity of the opioid system may be important in the modulation of affective state. Naloxone produces a conditioned place aversion in rodents, an effect that is centrally mediated. Previous pharmacological data using antagonists with preferential actions at mu-, delta-, and kappa-opioid receptors indicate the importance of the mu-opioid receptor in mediatin...