Retention of heroin and morphine–6β–glucuronide analgesia in a new line of mice lacking exon 1 of MOR–1

Schuller, Alwin G.; King, Michael A.; Zhang, Jiwen; Bolan, Elizabeth; Pan, Ying‐Xian; Morgan, Daniel J.; Chang, Albert; Czick, Maureen E.; Unterwald, Ellen M.; Pasternak, Gavril W.; Pintar, John E.

doi:10.1038/5706

Cited by 280 publications

(217 citation statements)

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“…The m-opioid receptor knockout and wild-type mice used for this experiment have been described previously and were on a mixed 129Sv/C57Bl6 background (Schuller et al, 1999). No detectable binding of [ 3 H]DAMGO or m-opioid receptor transcript was present in m-opioid receptor knockout mice and there is no evidence for compensatory changes in other opioid receptor subtypes: binding to dopioid receptor subtypes was comparable between genotypes and d-and k-and ORL-1 receptor mRNA levels were also unchanged (Schuller et al, 1999).…”

Section: L-opioid Receptor Knockout Micementioning

confidence: 99%

“…No detectable binding of [ 3 H]DAMGO or m-opioid receptor transcript was present in m-opioid receptor knockout mice and there is no evidence for compensatory changes in other opioid receptor subtypes: binding to dopioid receptor subtypes was comparable between genotypes and d-and k-and ORL-1 receptor mRNA levels were also unchanged (Schuller et al, 1999). Wild-type ( þ / þ ) and homozygous knockout (À/À) mice were obtained from heterozygous breeding.…”

Section: L-opioid Receptor Knockout Micementioning

confidence: 99%

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μ-Opioid Receptors are not Involved in Acute Cocaine-Induced Locomotor Activity nor in Development of Cocaine-Induced Behavioral Sensitization in Mice

Lesscher

Hordijk

Bondar

et al. 2004

Neuropsychopharmacol

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Although m-opioid receptors have been extensively investigated for their role in drug reinforcement, little is known about the contribution of these receptors to the acute and sensitized locomotor response to cocaine. In this study m-opioid receptor involvement in acute cocaine-induced locomotor activity and in the development of cocaine-induced behavioral sensitization was evaluated using mopioid receptor knockout mice and chronic naltrexone (NTX) pretreatment as models. In addition, co-administration of the specific mopioid receptor antagonist CTOP with repeated saline or cocaine injections was used to establish the involvement of m-opioid receptors in sensitization to the locomotor stimulant effects of cocaine. The acute locomotor response to cocaine (3, 10, 20, or 30 mg/kg i.p.) of mopioid receptor knockout or chronic NTX pretreated mice was not different from the cocaine response of their respective controls. With respect to cocaine-induced behavioral sensitization, induced by daily injections of 20 mg/kg cocaine for 11 subsequent days, mopioid receptor knockout mice developed behavioral sensitization to the locomotor stimulant effects of cocaine (challenge 10 mg/kg i.p.) comparable to wild-type littermates and the m-opioid receptor antagonist CTOP did not affect cocaine-induced sensitization either. However, mice that were pretreated with NTX exhibited augmented cocaine-induced behavioral sensitization relative to placebo pretreated controls, which may be ascribed to increased d-opioid receptor levels as has been described for chronic NTX pretreated mice. The present findings suggest that m-opioid receptors are not required for the acute locomotor response to cocaine nor are they essential for the development of cocaine-induced behavioral sensitization.

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Section: L-opioid Receptor Knockout Micementioning

confidence: 99%

Section: L-opioid Receptor Knockout Micementioning

confidence: 99%

μ-Opioid Receptors are not Involved in Acute Cocaine-Induced Locomotor Activity nor in Development of Cocaine-Induced Behavioral Sensitization in Mice

Lesscher

Hordijk

Bondar

et al. 2004

Neuropsychopharmacol

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“…Dissociation of the analgesic e ects of M6G and morphine has also been reported in knockout mice that lack either the ®rst or second exon of the MOR-1 gene (although we cannot con®rm this result in our laboratory, see Connor et al, 1999). It was found that M6G produced analgesia in mice homozygous for the exon 1 but not the exon 2 mutation, whereas morphine did not produce analgesia in mice homozygous for either mutation (Schuller et al, 1999). Binding studies using [ 3 H]-M6G have identi®ed two sites in calf and mouse brain: a low a nity site that corresponds to the classical mu-opioid receptor and a high a nity site that has a low a nity for morphine (Brown et al, 1997a,b).…”

Section: Introductionmentioning

confidence: 99%

Morphine‐6β‐glucuronide has a higher efficacy than morphine as a mu‐opioid receptor agonist in the rat locus coeruleus

Osborne

Chieng

Christie

2000

British J Pharmacology

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1 The pharmacological properties of the active morphine metabolite, morphine-6b-D-glucuronide (M6G), and the parent compound were compared in rat locus coeruleus neurons by electrophysiological recording in brain slices. 2 M6G and morphine activated potassium currents in voltage clamped neurons, which were blocked by the opioid receptor antagonist naloxone. 3 Both M6G and morphine behaved as partial agonists that produced maximal responses smaller than the system maximum, which was measured using [Met 5 ]-enkephalin. M6G produced a larger maximal response (78%) than morphine (62%), which we estimated was due to a 2 ± 4 fold di erence in the relative e cacy of the agonists. 4 3-O-methoxynaltrexone, which has been reported to behave as a selective antagonist of a M6G preferring receptor, was equally e ective at blocking currents produced by M6G and the selective mu-opioid receptor agonist DAMGO. 5 M6G currents were occluded by a prior application of morphine, and were reduced when muopioid receptors were desensitized by using [Met 5 ]-enkephalin. 6 Morphine-3b-D-glucuronide did not a ect action potential ®ring or membrane currents in locus coeruleus neurons and had no e ect on currents produced by M6G. 7 These results show that the relative e cacy of M6G is higher than morphine in locus coeruleus neurons, contrary to what has been shown using mu-opioid receptors expressed in cell clones.

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“…The clonal CHO cell line stably expressing HA-rMOR (CHO-HA-rMOR) was established and cultured as described previously [15], with a B max value of 1.8 pmol/mg membrane protein. MOR-knockout (K/O) mice were originally developed in the lab of Dr. John Pintar by disruption of exon-1 of the MOR-1 gene through homologous recombination [16]. Brains: the frozen meninges-stripped brains of mix-gender Sprague-Dawley rats were purchased from Pel-Freeze Biologicals (Rogers, AR).…”

Section: Introductionmentioning

confidence: 99%

Brain region-specific N-glycosylation and lipid rafts association of the rat mu opioid receptor

Huang

Chen

et al. 2008

Biochemical and Biophysical Research Communications

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The mu opioid receptor (MOR) in the rat and mouse caudate putamen (CPu) and thalamus was demonstrated as diffuse and broad bands by western blot with polyclonal antibodies against a Cterminal peptide of MOR, which were absent in the cerebellum and brains of MOR-knockout mice. The electrophoretic mobility of MOR differed in the two brain regions with median relative molecular masses (Mr's) of 75 kDa (CPu) vs. 66 kDa (thalamus) for the rat, and 74 kDa (CPu) vs. 63 kDa (thalamus) for the mouse, which was due to its differential N-glycosylation. Rat MOR in CPu was found mainly associated with low-density cholesterol-and ganglioside M1 (GM1)-enriched fractions (lipid rafts), while the MOR in the thalamus was present in rafts and non-rafts without preference. Cholesterol reduction by methyl-β-cyclodextrin decreased DAGMO-induced [ 35 S]GTPγS binding in rat CPu membranes to a greater extent than in the thalamus membranes.

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Retention of heroin and morphine–6β–glucuronide analgesia in a new line of mice lacking exon 1 of MOR–1

Cited by 280 publications

References 23 publications

μ-Opioid Receptors are not Involved in Acute Cocaine-Induced Locomotor Activity nor in Development of Cocaine-Induced Behavioral Sensitization in Mice

μ-Opioid Receptors are not Involved in Acute Cocaine-Induced Locomotor Activity nor in Development of Cocaine-Induced Behavioral Sensitization in Mice

Morphine‐6β‐glucuronide has a higher efficacy than morphine as a mu‐opioid receptor agonist in the rat locus coeruleus

Brain region-specific N-glycosylation and lipid rafts association of the rat mu opioid receptor

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