BACKGROUND AND PURPOSE Adenylyl cyclase sensitization occurs on chronic agonist activation of mu-opioid receptors and is manifested by an increase in cAMP levels (overshoot) on challenge with antagonist. It has been proposed that a long lasting constitutively active receptor is formed on chronic mu-opioid exposure and that antagonists with inverse agonist activity rapidly return the receptor to...

Morphine tolerance in vivo is reduced following blockade of the orphanin FQ/nociceptin (OFQ/N)/opioid receptor-like 1 (ORL1) receptor system, suggesting that OFQ/N contributes to the development of morphine tolerance. We previously reported that a 60-min activation of ORL1 receptors natively expressed in BE(2)-C cells desensitized both mu and ORL1 receptor-mediated inhibition of cAMP. Investiga...

mu opioid receptors are targets of native opioid peptides and addictive analgesic drugs. A major clinical liability of opiate drugs is their ability to cause physiological tolerance. Individual opiates, such as morphine and etorphine, differ both in their ability to promote physiological tolerance and in their effects on receptor regulation by endocytosis. Here, we demonstrate that arrestins pl...

Mu opioid receptors are densely expressed within rat striatum and are concentrated in anatomically discrete patches called striosomes. The density of striosomal mu receptors remains relatively constant during postnatal development, but little is known about their functional maturation. We examined the extent of G protein coupling by mu opioid receptors in rat brain during development, focusing ...

Opioid receptors in the ventral tegmental area, predominantly the mu-opioid receptors, have been suggested to modulate reinforcement sensitivity for both opioid and non-opioid drugs of abuse. The present study was conducted to study signal transduction proteins, which may mediate the functioning of mu-opioid receptors in the neurons of the ventral tegmental area. Therefore, brain slices of the ...

Biphalin, is a palindromic peptide [(Tyr-D-Ala-Gly-Phe-NH-)2] in which two opioid pharmacophores are connected "tail-to-tail". This peptide displays a broad affinity for all opioid receptors (mu, delta and kappa) as well as exceptionally high antinociceptive activity. Previous structure-activity studies demonstrated that one of the biphalin pharmacophores could be substituted with a hydrophobic...

Regulation of the mu-opioid receptor gene by opioid analgesic drugs has not been observed in rats and mice following in vivo treatments that produce tolerance. Although in vivo heterologous regulation of mu-opioid receptor mRNA by non-opioid compounds has been reported, the failure to observe changes in mu-opioid receptor mRNA levels in vivo after treatment with opioid agonists raised the possi...

Pharmacological approaches have defined the epsilon receptor as a beta-endorphin-preferring opioid receptor, described in rat vas deferens and in brain of several species. Only three opioid receptors-mu, delta and kappa-have been cloned and the existence of this additional subtype as a distinct protein remains controversial. Recently, the mouse brain epsilon receptor was detected in a G protein...

Intrathecal (i.t.) pretreatment with a low dose (0.3 nmol) of morphine causes an attenuation of i.t. morphine-produced analgesia; the phenomenon has been defined as morphine-induced antianalgesia. The opioid-produced analgesia was measured with the tail-flick (TF) test in male CD-1 mice. Intrathecal pretreatment with low dose (0.3 nmol) of morphine time dependently attenuated i.t. morphine-prod...

What is the neural correlate of preference that governs our spontaneous selection of visual information? With a rapid, event-related functional magnetic resonance imaging design, we showed that the viewing of highly preferred compared to less preferred scenes (as assessed by participant ratings) was associated with greater blood-oxygen level dependent responses in the right parahippocampal cort...