Pain is one of the most common and incapacitating symptoms experienced by patients with advanced cancer. Methadone is a potent opioid with strong affinity for the μ opioid receptor. In addition to being a potent μ opioid receptor ligand, methadone blocks the N-methyl-D-aspartic acid receptor and modulates neurotransmitters involved in descending pain modulation. These 3 properties enhance analg...

Mu- and delta-opioid subtype receptor antagonists were tested in the mouse for their effects on vertical climbing activity, an index of striatal dopaminergic activity. The selective delta-opioid antagonist ICI 154 129 (I/l) by itself enhanced vertical climbing activity in a dose-related manner, whereas the mu-opioid antagonist naloxone by itself was inactive on climbing behavior. Naloxone incre...

In vivo administration of μ-opioid receptor selective agonists to various species is known to suppress lymphocyte, NK cell, and macrophage functions, in addition to mediate pain relief and euphoria. Using a mouse model in which the μ-opioid receptor gene was disrupted by targeted homologous recombination, we explored the involvement of this receptor in natural killer (NK) cell activity and T ly...

Fusion proteins between a receptor and a pertussis toxininsensitive Gi subunit were used to gain insight into the molecular interactions that take place upon and opioid receptor heterodimerization. When opioid receptor-Gi1 fusions were coexpressed with nonfused opioid receptors in human embryonic kidney 293 cells, or vice versa, receptor heterodimers were detected by coimmunoprecipitation. In p...

Analysis of the distribution of mRNA encoding the serotonin (5-hydroxytryptamine) 5-HT(2A) receptor and the mu opioid peptide receptor in rat brain demonstrated their coexpression in neurons in several distinct regions. These regions included the periaqueductal gray, an area that plays an important role in morphine-induced analgesia but also in the development of tolerance to morphine. To explo...

In previous studies from our laboratory, chronic noncontingent morphine administration decreased mu opioid receptor-activated G-proteins in specific brainstem nuclei. In the present study, mu opioid receptor binding and receptor-activated G-proteins were examined after chronic heroin self-administration. Rats were trained to self-administer intravenous heroin for up to 39 d, achieving heroin in...

We have previously shown that the balance of electrically evoked descending brainstem control of spinal nociceptive reflexes undergoes a switch from excitation to inhibition in preadolescent rats. Here we show that the same developmental switch occurs when μ-opioid receptor agonists are microinjected into the rostroventral medulla (RVM). Microinjections of the μ-opioid receptor agonist [D-Ala(2...

Recent studies of knockout mice conclusively show that the mu opioid receptor mediates the analgesic effects of morphine; they further suggest that the mu opioid receptor also has a role in mediating the effects of other opioid agonists, and provide insights into the non-analgesic effects of mu opioids.

Coles, James A., Jr., Daniel C. Sigg, and Paul A. Iaizzo. Role of -opioid receptor activation in pharmacological preconditioning of swine. Am J Physiol Heart Circ Physiol 284: H2091–H2099, 2003. First published January 23, 2003; 10.1152/ajpheart.00843.2002.—Pharmacological preconditioning with -opioid receptor agonists is proarrhythmic and exerts antipreconditioning effects in rats. In swine, i...

Acute challenges with psychostimulants such as amphetamine affect impulsive behavior in both animals and humans. With regard to amphetamine, it is important to unravel how this drug affects impulsivity since it is not only a widely abused recreational drug but also regularly prescribed to ameliorate maladaptive impulsivity. Therefore, we studied the effects of amphetamine in two rat models of i...