Increased mu opioid receptor binding detected by PET in cocaine–dependent men is associated with cocaine craving

Zubieta, Jon-Kar; Gorelick, David A.; Stauffer, R.; Ravert, Hayden T.; Dannals, Robert F.; Frost, J. James

doi:10.1038/nm1196-1225

Cited by 247 publications

(157 citation statements)

References 29 publications

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“…In fact, we have reported that rats maintained on high-dose methadone maintenance show no cocaine-place preference and no cocaine-induced up-regulation of mu-opioid receptor mRNA in the nucleus accumbens core (Leri et al, 2006). This is notable because the effect of cocaine exposure on mu-opioid receptor density and function in mesocorticolimbic areas (Azaryan et al, 1996;Unterwald et al, 1992;Unterwald, 2001;Yuferov et al, 1999) has been associated to the intensity of cocaine cravings in humans (Gorelick et al, 2005;Zubieta et al, 1996), and to a variety of behavioral, electrophysiological and neurochemical responses to cocaine in animals (Mathon et al, 2005a(Mathon et al, , b, 2006Tang et al, 2005;Hummel et al, 2006).…”

Section: Discussionmentioning

confidence: 96%

High-Dose Methadone Maintenance in Rats: Effects on Cocaine Self-Administration and Behavioral Side Effects

Leri

Sorge

Cummins

et al. 2007

Neuropsychopharmacol

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It has been demonstrated that high-dose methadone maintenance is efficacious in reducing cocaine abuse in opioid-dependent individuals, but it is not clear whether this is caused by an action of methadone on the direct reinforcing properties of cocaine or on cocaine seeking. Also, it is not clear whether high-dose methadone maintenance may induce behavioral side effects, which could limit its clinical use. Here, we report that high-dose methadone maintenance (20-40 mg/kg/day) does not reduce, and even enhances cocaine (10-30 mg/kg, i.p.)-induced elevation in dopamine concentration in the ventral striatum measured by in vivo microdialysis. In parallel, however, rats maintained on high-dose methadone (30 mg/kg/day) seek and consume significantly less cocaine than controls when tested for intravenous cocaine (0.5 mg/kg/infusion) self-administration on a progressive ratio schedule of reinforcement. This reduction in cocaine self-administration does not result from impaired sensory-motor functioning as rats maintained on high-dose methadone show normal locomotor activity. Furthermore, the reduction in responding for cocaine does not seem to result from general behavioral deficits as male rats maintained on high methadone doses respond normally to palatable food and thermal pain, although their sexual responses to receptive females are greatly suppressed. Taken together, these results from studies in rats support the usefulness of larger doses of methadone to reduce severe cocaine abuse in opioid-dependent individuals and possibly in the management of pure-cocaine addiction.

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Section: Discussionmentioning

confidence: 96%

High-Dose Methadone Maintenance in Rats: Effects on Cocaine Self-Administration and Behavioral Side Effects

Leri

Sorge

Cummins

et al. 2007

Neuropsychopharmacol

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“…In humans, mu-opioid receptor binding detected by positron emission tomography (PET) using 11 C-carfentanil, has been demonstrated to be increased in several brain regions of cocaine addicts, after 1-4 days of abstinence (Zubieta et al 1996), and kappa-opioid receptor density measured autoradiographically has been demonstrated to be increased in brain tissue of cocaine overdose victims (Mash and Staley 1999).…”

Section: Discussionmentioning

confidence: 99%

Altered HPA Axis Responsivity to Metyrapone Testing in Methadone Maintained Former Heroin Addicts with Ongoing Cocaine Addiction

Schluger

Borg

et al. 2001

Neuropsychopharmacology

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“…Increases in OR binding have been associated with craving scores in cocaine-dependent volunteers undergoing cocaine withdrawal (Zubieta et al 1996). In a larger sample, it would be of interest to evaluate the relationship between OR binding potential in these regions and measures of withdrawal or craving for opiates.…”

Section: Discussionmentioning

confidence: 99%

Buprenorphine-Induced Changes in Mu-Opioid Receptor Availability in Male Heroin-Dependent Volunteers A Preliminary Study

Zubieta

Greenwald

Lombardi

et al. 2000

Neuropsychopharmacology

117

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Medications for the treatment of substance abuse may be developed for a variety of purposes (e.g., ameliorate toxicity, treat overdoses) but a primary goal is to attenuate the subjective, behavioral, or physiological effects of the drug of abuse. Buprenorphine is a high affinity, mu opioid partial agonist, with kappa antagonist action (Cowan et al. 1977;Heel et al. 1979;Lewis et al. 1983). This compound is being evaluated as an alternative to methadone maintenance and detoxification in the treatment of opioid dependence (Bickel and Amass 1995). Buprenorphine's mu receptor ( OR) agonist actions could reduce opiate craving and prevent withdrawal, thus improving compliance with treatment compared to conventional opiate receptor antagonists (e.g., naltrexone). At the same time, its partial efficacy and high affinity at OR's provide long lasting functional antagonism, making it an effective means of blocking the effects of abused opiates. This unique combination of NO . 3 Buprenorphine and Mu Receptor 327 pharmacological properties confers potential advantages, including enhanced safety over existing medications for treating opioid abuse (Lange et al. 1990).Buprenorphine sublingual (SL) liquid has been shown to decrease heroin self-administration in singledose human laboratory studies (Mello and Mendelson 1980;Mello et al. 1981Mello et al. , 1982; the dose-dependency of its effects on reinforcement has been less well characterized. In a clinical study, Johnson et al. (1995) compared the short-term efficacy of placebo, 2 and 8 mg/day buprenorphine in a parallel group, randomized design during a two-week initial maintenance period. In this study, active doses were more effective than placebo in decreasing heroin use, however, there were no differences in therapeutic efficacy between 2 and 8 mg. Schottenfeld et al. (1993) used a within-subject study design in which heroin-dependent outpatients received ascending/descending maintenance doses of buprenorphine ranging from 2 to 16 mg/day. Sixteen milligrams produced significant decreases in opioid-positive urine samples, relative to lower doses. Thus, available data suggest that, relative to placebo, buprenorphine doses ranging from 2 to 8 mg are equally capable of decreasing opioid use, whereas doses of 16 mg have greater efficacy. This may suggest that the effect of buprenorphine in decreasing opiate self-administration may not be dose-dependent, at least in lower dose ranges. In fact, in a recently completed laboratory study in heroindependent volunteers, maintenance doses of 2, 4, and 8 mg buprenorphine showed equal efficacy in decreasing the reinforcing effects of hydromorphone (Greenwald et al. 1999).On the other hand, laboratory studies have demonstrated that SL buprenorphine blocks many of the subjective effects of hydromorphone, a full mu opioid agonist, in a dose-dependent manner. For instance, Bickel et al. (1988) showed that maintenance on buprenorphine (2, 4, 8, 16 mg) produced dose-related decreases in subjective effects to cumulative hydromorphone (0, 6,...

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Increased mu opioid receptor binding detected by PET in cocaine–dependent men is associated with cocaine craving

Cited by 247 publications

References 29 publications

High-Dose Methadone Maintenance in Rats: Effects on Cocaine Self-Administration and Behavioral Side Effects

High-Dose Methadone Maintenance in Rats: Effects on Cocaine Self-Administration and Behavioral Side Effects

Altered HPA Axis Responsivity to Metyrapone Testing in Methadone Maintained Former Heroin Addicts with Ongoing Cocaine Addiction

Buprenorphine-Induced Changes in Mu-Opioid Receptor Availability in Male Heroin-Dependent Volunteers A Preliminary Study

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