Imaging Brain Mu-Opioid Receptors in Abstinent Cocaine Users: Time Course and Relation to Cocaine Craving

Gorelick, David A.; Kim, Yu Kyeong; Bencherif, Badreddine; Boyd, Susan J.; Nelson, Richard Alan; Copersino, Marc L.; Endres, Christopher J.; Dannals, Robert F.; Frost, J. James

doi:10.1016/j.biopsych.2005.02.026

Cited by 153 publications

(131 citation statements)

References 54 publications

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…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: 95%

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

Leri

Sorge

Cummins

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 95%

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

Leri

Sorge

Cummins

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Acute oral amphetamine administration has been shown to induce endogenous opioid release in many brain regions frequently implicated in addiction, including the basal ganglia, frontal cortex areas, thalamus, and striatum (Colasanti et al, 2012;Mick et al, 2014). Further, elevated frontal/temporal cortical μ-opioid receptor binding has been observed in cocaine dependence, the degree of which was shown to positively correlate with self-reported cocaine craving (Gorelick et al, 2005), and relate to relapse following treatment (Ghitza et al, 2010;Gorelick et al, 2008). NTX has been shown to block ethanol-induced β-endorphin and subsequent dopamine release in the nucleus accumbens and provide a blockade of ethanol-induced β-endorphin inhibition of GABAergic inhibitory interneurons in the ventral tegmental area (Johnson, 2008;Zalewska-Kaszubska et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Ray

Bujarski

Courtney

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatmentseeking individuals meeting DSM-IV criteria for MA abuse or dependence (n = 30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of 'crave drug,' 'stimulated,' and 'would like drug access,' decreased the the post-MA administration timecourse of 'anxious' and increased ratings of 'bad drug effects,' as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA.

show abstract

“…A key modulator of the dopaminergic system is the mu opioid receptor (MOR), and opiate receptor antagonists have some efficacy in treating GD. Higher MOR availability has been reported in studies by using [ 11 C]carfentanil or [ 11 C]diprenorphine PET in cocaine, opiate and alcohol addiction (Gorelick et al 2005; Heinz et al 2005; Williams et al 2007; Williams et al 2009). However, we recently reported no difference in [ 11 C]carfentanil binding in individuals with GD (Mick et al 2015).…”

Section: Introductionmentioning

confidence: 86%

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

et al. 2016

View full text Add to dashboard Cite

As a behavioural addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours, and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. This study therefore investigated GABAA receptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [11C]Ro15‐4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity. We found significantly higher [11C]Ro15‐4513 total distribution volume (VT) in the right hippocampus in the GD group compared with HV. We found higher levels of the ‘Negative Urgency’ construct of impulsivity in GD, and these were positively associated with higher [11C]Ro15‐4513 VT in the amygdala in the GD group; no such significant correlations were evident in the HV group. These results contrast with reduced binding of GABAergic PET ligands described previously in alcohol and opiate addiction and add to growing evidence for distinctions in the neuropharmacology between substance and behavioural addictions. These results provide the first characterization of GABAA receptors in GD with [11C]Ro15‐4513 PET and show greater α5 receptor availability and positive correlations with trait impulsivity. This GABAergic dysregulation is potential target for treatment.

show abstract

Imaging Brain Mu-Opioid Receptors in Abstinent Cocaine Users: Time Course and Relation to Cocaine Craving

Cited by 153 publications

References 54 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

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

Contact Info

Product

Resources

About