Antinociceptive Interactions between Mu-Opioid Receptor Agonists and the Serotonin Uptake Inhibitor Clomipramine in Rhesus Monkeys: Role of Mu Agonist Efficacy

Banks, Matthew L.; Rice, Kenner C.; Negus, S. Stevens

doi:10.1124/jpet.110.169276

Cited by 29 publications

(38 citation statements)

References 36 publications

(68 reference statements)

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“…This difference between methadone and morphine may be related to their different efficacies as mu agonists. Specifically, morphine has lower efficacy than methadone as a mu agonist (Selley et al, 1998), and this lower efficacy results in both shallower dose-effect curves and greater potency differences for production of different effects (e.g., Banks et al, 2010). Consequently, use of morphine may have facilitated detection of mu agonist-induced increases in cocaine choice at doses that did not eliminate responding or produce other dose-limiting side effects.…”

Section: Discussionmentioning

confidence: 99%

Maintenance on naltrexone + amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys

Moerke

Banks

Cheng

et al. 2017

Drug and Alcohol Dependence

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Background Cocaine use disorder remains a significant public health issue for which there are no FDA-approved pharmacotherapies. Amphetamine maintenance reduces cocaine use in preclinical and clinical studies, but the mechanism of this effect is unknown. Previous studies indicate a role for endogenous opioid release and subsequent opioid receptor activation in some amphetamine effects; therefore, the current study examined the role of mu-opioid receptor activation in d-amphetamine treatment effects in an assay of cocaine-vs-food choice. Methods Adult male rhesus monkeys with double-lumen intravenous catheters responded for concurrently available food pellets and cocaine injections (0–0.1 mg/kg/injection) during daily sessions. Cocaine choice and overall reinforcement rates were evaluated during 7-day treatments with saline or test drugs. Results During saline treatment, cocaine maintained a dose-dependent increase in cocaine-vs.-food choice. The mu-opioid receptor agonist morphine (0.032–0.32 mg/kg/h) dose-dependently increased cocaine choice and decreased rates of reinforcement. A dose of the mu-selective opioid receptor antagonist naltrexone (0.0032 mg/kg/h) that completely blocked morphine effects had no effect on cocaine choice when it was administered alone, but it enhanced the effectiveness of a threshold dose of 0.032 mg/kg/h amphetamine to decrease cocaine choice without also enhancing nonselective behavioral disruption by this dose of amphetamine. Conversely, the kappa-selective opioid antagonist norbinalorphimine did not enhance amphetamine effects on cocaine choice. Conclusions These results suggest that amphetamine maintenance produces mu opioid-receptor mediated effects that oppose its anti-cocaine effects. Co-administration of naltrexone may selectively enhance amphetamine potency to decrease cocaine choice without increasing amphetamine potency to produce general behavioral disruption.

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Section: Discussionmentioning

confidence: 99%

Maintenance on naltrexone + amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys

Moerke

Banks

Cheng

et al. 2017

Drug and Alcohol Dependence

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“…The following are among the adjuncts that have been demonstrated to selectively enhance m-opioid antinociception over rate suppression: selective serotonin uptake inhibitors (Gatch et al, 1998;Banks et al, 2010), a d-opioid receptor agonist (Stevenson et al, 2003), an N-Methyl-Daspartate antagonist (Fischer and Dykstra, 2006), metabotropic glutamate receptor 1 and metabotropic glutamate receptor 2/3 antagonists (Fischer et al, 2008), and cannabinoids (Maguire and France, 2014). Interestingly, in some cases, greater antinociceptive enhancement of low-compared to high-efficacy m agonists was reported (Gatch et al, 1998;Banks et al, 2010), whereas in other cases, the opposite was found (Maguire and France, 2014). These studies represent promising potential novel pain therapies; however, subsequent clinical testing of these therapies has not been performed.…”

Section: Discussionmentioning

confidence: 99%

Antinociceptive Interactions between the Imidazoline I2 Receptor Agonist 2-BFI and Opioids in Rats: Role of Efficacy at the -Opioid Receptor

Jn¹,

Obeng

Zhang

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Although m-opioids have been reported to interact favorably with imidazoline I 2 receptor (I 2 R) ligands in animal models of chronic pain, the dependence on the m-opioid receptor ligand efficacy on these interactions had not been previously investigated. This study systematically examined the interactions between the selective I 2 receptor ligand 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI) and three m-opioid receptor ligands of varying efficacies: fentanyl (high efficacy), buprenorphine (medium-low efficacy), and 17-cyclopropylmethyl-3,14b-dihydroxy-4,5a-epoxy-6a-[(39-isoquinolyl) acetamido] morphine (NAQ; very low efficacy). The von Frey test of mechanical nociception and Hargreaves test of thermal nociception were used to examine the antihyperalgesic effects of drug combinations in complete Freund's adjuvant-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to examine the rate-suppressing effects of each drug combination. Dose-addition and isobolographical analyses were used to characterize the nature of drug-drug interactions in each assay. 2-BFI and fentanyl fully reversed both mechanical and thermal nociception, whereas buprenorphine significantly reversed thermal but only slightly reversed mechanical nociception. NAQ was ineffective in both nociception assays. When studied in combination with fentanyl, NAQ acted as a competitive antagonist (apparent pA 2 value: 6.19). 2-BFI/fentanyl mixtures produced additive to infra-additive analgesic interactions, 2-BFI/buprenorphine mixtures produced supra-additive to infra-additive interactions, and 2-BFI/NAQ mixtures produced supra-additive to additive interactions in the nociception assays. The effects of all combinations on schedule-controlled responding were generally additive. Results consistent with these were found in experiments using female rats. These findings indicate that lower-efficacy m-opioid receptor agonists may interact more favorably with I 2 R ligands than high-efficacy m-opioid receptor agonists.

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“…Accumulating evidence suggests that drugs acting on 5-HT systems might be particularly useful for treating pain when they are used in combination with opioids. For example, the SSRIs fluoxetine and clomipramine potentiate the antinociceptive effects of morphine in rats and rhesus monkeys (Larson and Takemori 1977; Hynes et al 1985; Gatch et al 1998; Banks et al 2010), and the 5-HT releaser fenfluramine increases the antinociceptive effects of morphine in monkeys (Li et al 2011) and the analgesic effects of morphine in humans (Coda et al 1993). Agonists acting selectively on 5-HT receptor subtypes have also been shown to enhance the antinociceptive effects of opioids.…”

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confidence: 99%

Effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and quipazine on heroin self-administration in rhesus monkeys

Maguire

Koek

2012

Psychopharmacology

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Rationale The serotonin (5-HT) system is involved in pain modulation, and 5-HT receptor agonists can enhance antinociceptive effects of mu opioid receptor agonists. Less is known about the actions of 5-HT receptor agonists on other effects of opioids. Objective This study examined the effects of non-contingent and contingent administration of the 5-HT2A receptor agonists DOM and quipazine on i.v. heroin self-administration in rhesus monkeys. Results Heroin (0.0001-0.1 mg/kg/infusion) generated an inverted U-shaped dose-response function. Non-contingent administration of DOM (0.1-0.32 mg/kg) flattened the dose-response function in three monkeys and eliminated heroin self-administration in a fourth monkey. Contingent DOM (0.0032-0.032 mg/kg/infusion) alone did not maintain responding above that maintained by saline, and, when added to self-administered heroin, monkeys responded less than for the same unit doses of heroin alone. Non-contingent (0.32-3.2 mg/kg) and contingent (0.0032-0.56 mg/kg/infusion) administration of quipazine flattened the dose-response function in two monkeys, increasing responding maintained by small unit doses of heroin and saline, but failed to enhance responding for heroin in two other monkeys. Conclusion This study shows that DOM does not enhance, and might attenuate, the positive reinforcing effects of the mu opioid receptor agonist heroin. Quipazine increased responding for saline and small doses of heroin; those effects were modest and observed in only two subjects. Taken together, these data suggest that 5-HT2A receptor agonists do not significantly enhance the reinforcing effectiveness of mu opioid receptor agonists and support the view that administering 5-HT drugs in combination with opioids to treat pain might not enhanced abuse liability.

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Antinociceptive Interactions between Mu-Opioid Receptor Agonists and the Serotonin Uptake Inhibitor Clomipramine in Rhesus Monkeys: Role of Mu Agonist Efficacy

Cited by 29 publications

References 36 publications

Maintenance on naltrexone + amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys

Maintenance on naltrexone + amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys

Antinociceptive Interactions between the Imidazoline I2 Receptor Agonist 2-BFI and Opioids in Rats: Role of Efficacy at the -Opioid Receptor

Effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and quipazine on heroin self-administration in rhesus monkeys

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