μ Opiate Receptor Gene Dose Effects on Different Morphine Actions Evidence for Differential in vivo μ Receptor Reserve

Sora, Ichiro; Elmer, Gregory I.; Funada, Masahiko; Pieper, Jeanne O.; Li, Xiao Fei; Hall, F. Scott; Uhl, George R.

doi:10.1016/s0893-133x(00)00252-9

Cited by 133 publications

(133 citation statements)

References 46 publications

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…These results provide a sharp contrast to the virtually complete loss of rewarding effects of morphine in place preference assays using either these or other strains of homozygous MOR-KO mice (Matthes et al, 1996;Sora et al, 2001). Our current observations that the rewarding effects of buprenorphine in homozygous MOR-KO mice were abolished by pretreatment with naloxone, a nonselective opioid antagonist, suggest d-and/or k-opioid receptor involvement.…”

Section: Effects Of Buprenorphine In Mor-ko Micecontrasting

confidence: 51%

“…Wild-type, heterozygous, and homozygous MOR-KO mouse littermates from crosses of heterozygous/heterozygous MOR-KO mice with a C57BL/6J genetic background, as described previously (Sora et al, 2001), served as subjects. The experimental procedures and housing conditions were approved by the Institutional Animal Care and Use Committee, and all animals were cared for and treated humanely in accordance with our institutional animal experimentation guidelines.…”

Section: Methods Animalsmentioning

confidence: 99%

“…The precise molecular mechanisms underlying the therapeutic and rewarding effects of buprenorphine have not been clearly delineated, although investigators have estimated its antinociceptive and rewarding effects by using selective agonists and antagonists. Recent success in developing knockout mice with mopioid receptor gene deletions have allowed definition of the loss of the analgesic and rewarding effects of morphine that occurs in mice in the absence of m-opioid receptors (Kieffer, 1999;Loh et al, 1998;Sora et al, 1997bSora et al, , 2001. DPDPE, an agonist active at d-opioid receptors with some affinity for m-opioid receptors, has a much weaker analgesic effect in homozygous m-opioid receptor knockout (MOR-KO) mice (Matthes et al, 1998;Sora et al, 1997a).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Buprenorphine Antinociception is Abolished, but Naloxone-Sensitive Reward is Retained, in μ-Opioid Receptor Knockout Mice

Ide

Minami

Satoh

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

Buprenorphine is a relatively nonselective opioid receptor partial agonist that is used in the management of both pain and addiction. To improve understanding of the opioid receptor subtypes important for buprenorphine effects, we now report the results of our investigation on the roles of m-, d-, and k-opioid receptors in antinociceptive responses and place preferences induced by buprenorphine. Buprenorphine antinociception, assessed by hot-plate and tail-flick tests, was significantly reduced in heterozygous m-opioid receptor knockout (MOR-KO) mice and abolished in homozygous MOR-KO mice. In contrast, buprenorphine retained its ability to establish a conditioned place preference (CPP) in homozygous MOR-KO, although the magnitude of place preference was reduced as the number of copies of wild-type m-opioid receptor genes was reduced. The remaining CPP of buprenorphine was abolished by pretreatment with the nonselective opioid antagonist naloxone, but only partially blocked by pretreatment with either the d-selective opioid antagonist naltrindole or the k-selective opioid antagonist norbinaltorphimine. These data, and biochemical confirmation of buprenorphine actions as a partial d-, m-, and k-agonist, support the ideas that m-opioid receptors mediate most of analgesic properties of buprenorphine, but that m-and d-and/or k-opioid receptors are each involved in the rewarding effects of this drug.

show abstract

Section: Effects Of Buprenorphine In Mor-ko Micecontrasting

confidence: 51%

Section: Methods Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Buprenorphine Antinociception is Abolished, but Naloxone-Sensitive Reward is Retained, in μ-Opioid Receptor Knockout Mice

Ide

Minami

Satoh

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Genetic studies using knockout mice lacking MORÀ/À support this view: morphine-conditioned place preference (CPP) and intravenous morphine self-administration are abolished in MORÀ/À mice (Matthes et al, 1996;Becker et al, 2000;Sora et al, 2001). In contrast, the contribution of d-opioid receptors (DORs) to opiate reward remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Brain Regional Fos Expression Elicited by the Activation of μ- but not δ-Opioid Receptors of the Ventral Tegmental Area: Evidence for an Implication of the Ventral Thalamus in Opiate Reward

David

Matifas

Gavello-Baudy

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Both m-opioid receptors (MORs) and d-opioid receptors (DORs) are expressed in the ventral tegmental area (VTA) and are thought to be involved in the addictive properties of opiates. However, their respective contributions to opiate reward remain unclear. We used intracranial self-administration (ICSA) to study the rewarding effects of morphine microinjections into the VTA of male and female MORÀ/À and DORÀ/À mice. In brains of mice tested for intra-VTA morphine self-administration, we analyzed regional Fos protein expression to investigate the neural circuitry underlying this behavior. Male and female WT and DORÀ/À mice exhibited similar selfadministration performances, whereas knockout of the MOR gene abolished intra-VTA morphine self-administration at all doses tested. Naloxone (4 mg/kg) disrupted this behavior in WT and DOR mutants, without triggering physical signs of withdrawal. Morphine ICSA was associated with an increase in Fos within the nucleus accumbens, striatum, limbic cortices, amygdala, hippocampus, the lateral mammillary nucleus (LM), and the ventral posteromedial thalamus (VPM). This latter structure was found to express high levels of Fos exclusively in self-administering WT and DORÀ/À mice. Abolition of morphine reward in MORÀ/À mice was associated with a decrease in Fos-positive neurons in the mesocorticolimbic dopamine system, amygdala, hippocampus (CA1), LM, and a complete absence within the VPM. We conclude that (i) VTA MORs, but not DORs, are critical for morphine reward and (ii) the role of VTA-thalamic projections in opiate reward deserves to be further explored.

show abstract

“…The neurobiological actions of opiates have been widely studied, and it appears that the rewarding effects of heroin and its psychoactive metabolites, e.g., morphine, are strongly mediated via the opioid receptor (MOR). A line of compelling evidence obtained from experimental transgenic animal studies has documented that the reinforcing and locomotor behavioral properties of morphine are abolished in animals deficient in the MOR (2,3). The localization of MORs to limbic and motor neural circuits that are tightly linked to addiction disorders (4,5) also emphasizes the importance of the MOR in heroin dependence.…”

mentioning

confidence: 99%

μ Opioid receptor A118G polymorphism in association with striatal opioid neuropeptide gene expression in heroin abusers

Drakenberg¹,

Nikoshkov²,

Horváth

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

Opioid receptors are critical for heroin dependence, and A118G SNP of the opioid receptor gene (OPRM1) has been linked with heroin abuse. In our population of European Caucasians (n ‫؍‬ 118), Ϸ90% of 118G allelic carriers were heroin users. Postmortem brain analyses showed the OPRM1 genotype associated with transcription, translation, and processing of the human striatal opioid neuropeptide system. Whereas down-regulation of preproenkephalin and preprodynorphin genes was evident in all heroin users, the effects were exaggerated in 118G subjects and were most prominent for preproenkephalin in the nucleus accumbens shell. Reduced opioid neuropeptide transcription was accompanied by increased dynorphin and enkephalin peptide concentrations exclusively in 118G heroin subjects, suggesting that the peptide processing is associated with the OPRM1 genotype. Abnormal gene expression related to peptide convertase and ubiquitin͞proteosome regulation was also evident in heroin users. Taken together, alterations in opioid neuropeptide systems might underlie enhanced opiate abuse vulnerability apparent in 118G individuals.drug abuse ͉ dynorphin ͉ enkephalin ͉ mRNA

show abstract

μ Opiate Receptor Gene Dose Effects on Different Morphine Actions Evidence for Differential in vivo μ Receptor Reserve

Abstract: Homozygous transgenic knockout mice without -opioid receptors lack morphine-induced antinociception

Cited by 133 publications

References 46 publications

Buprenorphine Antinociception is Abolished, but Naloxone-Sensitive Reward is Retained, in μ-Opioid Receptor Knockout Mice

Buprenorphine Antinociception is Abolished, but Naloxone-Sensitive Reward is Retained, in μ-Opioid Receptor Knockout Mice

Brain Regional Fos Expression Elicited by the Activation of μ- but not δ-Opioid Receptors of the Ventral Tegmental Area: Evidence for an Implication of the Ventral Thalamus in Opiate Reward

μ Opioid receptor A118G polymorphism in association with striatal opioid neuropeptide gene expression in heroin abusers

Contact Info

Product

Resources

About