Upregulation of opioid receptor subtypes correlates with potency changes of morphine and dadle

Yoburn, Byron C.; Luke, Markham C.; Pasternak, Gavril W.; Inturrisi, Charles E.

doi:10.1016/0024-3205(88)90587-5

Cited by 61 publications

(18 citation statements)

References 9 publications

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“…The data on calcium channel blockers and blood pressure-lowering drugs having discontinuation effects and the data suggesting the speculation about rebound hypertension after discontinuing ␣-adrenergic receptor antagonists have been presented above. Yoburn et al (1988) found that treatment of mice for 1 week with naltrexone, an opioid receptor antagonist, up-regulated all classes of opioid receptors. After naltrexone was stopped, they found supersensitivity to opioid administration, a drug discontinuation effect.…”

Section: Withdrawal Syndromesmentioning

confidence: 99%

Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

Reidenberg¹

2011

J Pharmacol Exp Ther

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Most reviews of drug withdrawal effects focus on drugs of potential abuse such as opioids, benzodiazepines, etc. Abrupt discontinuation of many other drugs used in medicine cause withdrawal syndromes, some of which can be fatal. Discontinuation of a number of cardiovascular drugs can increase risk of cardiovascular events above that of people not taking these drugs. These include ␤-adrenergic receptor antagonists, aspirin, HMG-CoA reductase inhibitors (statins), and heparin. Rebound hypertension occurs after abrupt cessation of many antihypertensive drugs. The possibility of discontinuation syndromes has usually been neglected until adverse clinical events force them to be noticed. Attention to the possibility of drug discontinuation effects is an important part of drug safety evaluation.

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Section: Withdrawal Syndromesmentioning

confidence: 99%

Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

Reidenberg¹

2011

J Pharmacol Exp Ther

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“…The selectivity of the upregulation depends on the opioid antagonist dose: with low antagonist doses, only the number of µ-sites is increased, while higher doses up-regulate also δ-and κ-sites ). Up-regulation of opioid binding sites has been shown to be accompanied by an increased sensitivity to the antinociceptive (Tempel et al 1985;Yoburn et al 1986Yoburn et al , 1988Yoburn et al , 1989Millan et al 1988;Paronis and Holtzman 1991) and reinforcing effects of morphine (Bardo and Neisewander 1987), and a potentiation of morphine effects on dopamine synthesis and metabolism (Ahtee et al 1990), suggesting that up-regulation is of functional significance. However, data on the effects of the sensitized opioid system on alcohol behaviours after chronic opioid antagonist administration have so far been lacking, although it is known that a single naltrexone dose (50 mg) produces a complete blockade of at least µ-opioid receptors in the human brain for more than 24 h (Lee et al 1988).…”

Section: Introductionmentioning

confidence: 95%

“…Gradual and persistent decreases of alcohol consumption after repeated opioid antagonist injections have also been reported in rats (Hubbell et al 1986;Sinclair 1992;Wegelius et al 1994), but administration of antagonists via subcutaneous pellets has been found to increase alcohol intake, especially in rodent lines with a high innate alcohol preference, such as C57BL/6 mice and Syracuse high avoidance rats (Iso and Brush 1991;Phillips et al 1997). Chronic administration of either naloxone or naltrexone has reliably been demonstrated to transiently increase the number of opioid binding sites in the rodent brain (Zukin et al 1982;Tempel et al 1984Tempel et al , 1985Yoburn et al 1986Yoburn et al , 1988Yoburn et al , 1989Morris et al 1988). The selectivity of the upregulation depends on the opioid antagonist dose: with low antagonist doses, only the number of µ-sites is increased, while higher doses up-regulate also δ-and κ-sites ).…”

Section: Introductionmentioning

confidence: 96%

Effects of continuous opioid receptor blockade on alcohol intake and up-regulation of opioid receptor subtype signalling in a genetic model of high alcohol drinking

Hyytiä¹,

Ingman

Soini

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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Effects of a continuous naloxone infusion via osmotic pumps on alcohol drinking and opioid receptor density and function in the high-drinking AA (Alko, Alcohol) rats were examined. AA rats were trained to drink 10% (v/v) ethanol in a 1-h limited access procedure and implanted with subcutaneous osmotic pumps delivering either saline, a low dose (0.3 mg/kg per hour), or a high dose (3.0 mg/kg per hour) of naloxone for 7 days. The pumps were then removed and alcohol, food and water intakes were measured for another 4 days. Compared with saline, both naloxone doses significantly suppressed 1-h alcohol intake during the 7-day infusion. The suppression was smaller than that by a bolus injection of the same daily dose 15 min before the session, although a complete blockade of morphine-induced antinociception was achieved even with the smaller naloxone infusion. Significant decreases were also seen in daily food and water intake during the first days, but they quickly returned to their previous baselines. After pump removal, rats of both naloxone-treated groups rapidly increased their alcohol drinking and reached the pretreatment baseline, while their food and water intakes significantly surpassed their baselines. Naloxone infusion at 3.0 mg/kg per hour for 7 days significantly decreased 24-h alcohol drinking without affecting alcohol preference. Twenty-four hours after pump removal, autoradiography with [3H]DAMGO, [3H]DPDPE and [3H]U-69,543 revealed an up-regulation of mu-, delta- and kappa-opioid receptor binding sites in many brain areas of these animals. This receptor up-regulation was functional, because receptor coupling to G-protein activation was enhanced by agonist ligands, as revealed by [35S]GTPgammaS autoradiography. A good correlation existed between ligand binding densities and G-protein activation for mu- and kappa-receptors in control and naloxone-treated brain sections. Furthermore, morphine-induced analgesia in a hot-plate test showed a leftward shift in the morphine dose-response curve after naloxone treatment. These results suggest that the usefulness of a chronic opioid antagonist dosing regime could be limited by nonspecific effects of the antagonist on ingestive behaviour, an up-regulation of opioid receptors with high antagonist doses, and the resulting supersensitivity to opioid agonists after the discontinuation of the treatment.

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“…The possible role of m-opioid receptors in the acute locomotor response to cocaine and in cocaine-induced behavioral sensitization was investigated using m-opioid receptor knockout mice, co-administration of the m-opioid receptor selective antagonist CTOP (Hawkins et al, 1989), and by means of chronic NTX pretreated mice. Chronic NTX pretreatment was included in this study because chronic exposure of mice to NTX results in an increase in mopioid receptor binding sites, although d-opioid receptor binding is also increased by this pretreatment albeit to a lower extent and upregulation of k-opioid receptors after chronic NTX exposure is restricted to cortical regions (Yoburn et al, 1988;Lesscher et al, 2003).…”

Section: Introductionmentioning

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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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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Upregulation of opioid receptor subtypes correlates with potency changes of morphine and dadle

Cited by 61 publications

References 9 publications

Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

Effects of continuous opioid receptor blockade on alcohol intake and up-regulation of opioid receptor subtype signalling in a genetic model of high alcohol drinking

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

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