Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers

Abstract

Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [11C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [11C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [11C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [11C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions.

Suggestive association between OPRM1 and impulse control disorders in Parkinson's disease

“…A decreased receptor function associated with a protective effect of ICDs and related behaviors in PD is in accordance with a recent clinical trial suggesting therapeutic efficacy of naltrexone, a mu opioid receptor antagonist, on ICDs in PD. 30 PET studies have shown blunted endogenous opioid release following amphetamine challenge in pathological gamblers 31 and decreased availability of mu opioid receptors in different brain areas in pathological gambling and binge eating. 32 However, the mechanisms by which rs1799971 alters mu opioid receptor function and its potential role in addictive behaviors remain to be fully understood.…”

Aerobic exercise modulates anticipatory reward processing via the μ‐opioid receptor system

“…Decrease in BP ND is often interpreted as evidence of increased concentration of endogenous neurotransmitter, according to the competition principle. This principle has been most robustly established for the dopamine system (Laruelle, ) but has been more recently used also for the µ‐opioid system (Colasanti et al, ; Mick et al, ). Although we found significant correlations between exercise‐induced change in BP ND and change in anticipatory food reward activations, not all subjects demonstrated decreased BP ND consistent with endogenous opioid release; in fact, most subjects showed increased BP ND after exercise.…”

Naltrexone in the Treatment of Broadly Defined Behavioral Addictions: A Review and Meta-Analysis of Randomized Controlled Trials

“…The impulsivity that seems to characterize addiction may be caused by disruptions within the opioid system. Mouse µ receptor knockout models show remarkably decreased motor impulsivity [29] and higher µ receptor availability has been associated with greater impulsivity [30]. Hence, naltrexone, as µ receptor antagonist, through reducing impulsivity may be effective across a rather broad spectrum of addictions involving both broadly defined behavioral addictions and substance use disorders.…”