Congenic C57BL/6 µ opiate receptor (MOR) knockout mice: baseline and opiate effects

Hall, F. Scott; Li, X.-F.; Goeb, Michelle; Roff, Shannon; Hoggatt, H.; Sora, Ichiro; Uhl, George R.

doi:10.1034/j.1601-183x.2003.00016.x

Cited by 41 publications

(39 citation statements)

References 48 publications

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“…Since the behaviorally relevant diffusional spread occurring in the conditions of this study can be estimated as 600 mm laterally and 800 mm dorsally to the injection site, VTA opioid receptors are likely to be the main target of the drug (David and Cazala, 1994a, b). These results are consistent with the previous pharmacological and genetic studies supporting an involvement of MORs in opiate reward (Matthes et al, 1996; Bardo, 1998; Shippenberg and VTA opioid receptors, reward and fos protein expression V David et al Elmer, 1998;van Ree et al, 1999;Chefer et al, 2003;Hall et al, 2003). Although preferentially a m-agonist, morphine also binds DORs with sub-mM affinity.…”

Section: Discussionsupporting

confidence: 89%

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

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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.

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Section: Discussionsupporting

confidence: 89%

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

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“…However, these increases were far smaller than might be anticipated from the reduction in their receptor-binding sites (Table 1), suggesting spare receptors. A similar lack of correlation between the receptor density and analgesic response was previously observed in heterozygous mice from Oprm1 KO mouse lines (33,34).…”

Section: Targeting Intracellular Carboxyl Termini Of the Mu Opioid Rementioning

confidence: 54%

“…This was particularly interesting in view of the lack of change in morphine analgesia among the truncation models, despite receptor binding decreases of 30% to 50% in mE4M and mE3M models. Maintaining analgesic activity with reduced receptor expression has been reported previously in mu receptor KO models in which loss of half the receptor in the heterozygotes failed to change morphine's analgesic ED 50 values (33,34). Removal of the exon 4-encoded 12 aa in mMOR-1, the predominant 7TM variant, facilitated morphine tolerance in mE4M homozygous mice on both B6 and 129 backgrounds, implying that expression of the exon 4-encoded sequence impedes the development of morphine tolerance.…”

Section: Discussionmentioning

confidence: 95%

Alternatively spliced mu opioid receptor C termini impact the diverse actions of morphine

Xu¹,

Lu²,

Narayan³

et al. 2017

Journal of Clinical Investigation

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“…In spite of intensive study, the causative genetic variation that underlies Mop2 has yet to be identified. Oprm knockout mice on the B6 genetic background exhibit lack of morphineinduced analgesia, locomotor activity, and conditioned place preference (Hall et al, 2003). Oprm knockout mice have also been shown to lack robust responsiveness in intracerebroventricular morphine self-administration studies (Becker et al, 2000); however, this latter study did not control for genetic background and did not test responsiveness of knockout mice in a voluntary drinking paradigm.…”

Section: Discussionmentioning

confidence: 77%

Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains

Ferraro

Golden

Smith

et al. 2004

Neuropsychopharmacol

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C57BL/6 (B6) and DBA/2 (D2) mice exhibit disparate behavior when tested for voluntary morphine intake in a two-bottle choice drinking paradigm with B6 mice consuming 10 times more drug than D2 mice. Previous genetic mapping studies identified a locus, Mop2, on the proximal part of chromosome 10 that explained over half of the genetic variance in this mouse model of opioid selfadministration. We constructed a set of reciprocal congenic strains between B6 and D2 mice in which the proximal portion of chromosome 10 has been introgressed from one strain onto the background of the other. We tested mice from this pair of reciprocal strains together with progenitor B6 and D2 mice in a two-bottle choice drinking paradigm with morphine and quinine. The results showed that introgression of chromosome 10 alleles from the B6 strain onto a D2 genetic background increased voluntary morphine intake four-fold compared to progenitor D2 mice. Preference for morphine was also increased significantly in D2.B6-Mop2 mice compared to progenitor D2 mice. Conversely, introgression of chromosome 10 alleles from the D2 strain onto a B6 genetic background decreased morphine intake by half compared to progenitor B6 mice in B6.D2 -Mop2 mice; however, high morphine preference was maintained in this congenic strain most likely due to strong quinine aversion. When quinine was eliminated from the control bottle, morphine preference in B6.D2-Mop2 mice was decreased significantly relative to B6 and D2.B6-Mop2 mice. Overall, these data confirm the existence of a gene(s) on chromosome 10 proximal to D10Mit124 that has a strong influence on the difference in morphine drinking behavior between B6 and D2 mice.

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Congenic C57BL/6 µ opiate receptor (MOR) knockout mice: baseline and opiate effects

Cited by 41 publications

References 48 publications

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

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

Alternatively spliced mu opioid receptor C termini impact the diverse actions of morphine

Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains

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