Deficits in Dopamine D2 Receptors and Presynaptic Dopamine in Heroin Dependence: Commonalities and Differences with Other Types of Addiction

Abstract

Background Positron Emission tomography (PET) imaging studies have shown that addiction to a number of substances of abuse is associated with a decrease in dopamine D2/3 receptor binding and decreased pre-synaptic dopamine release in the striatum. Some studies have also shown that these reductions are associated with the severity of addiction. For example, in cocaine dependence, low dopamine release is associated with the choice to self-administer cocaine. The goal of the present study was to investigate these parameters of striatal dopamine transmission in heroin dependence and their association with drug seeking behavior. Methods Heroin dependent and healthy control subjects were scanned with [11C]raclopride before and after stimulant administration (methylphenidate) to measure striatal D2/3 receptor binding and pre-synaptic dopamine release. Following the PET scans, the heroin dependent subjects performed heroin self-administration sessions. Results Both striatal D2/3 receptor binding and dopamine release were reduced in the heroin dependent subjects compared to healthy controls. However, neither PET measure of dopamine transmission predicted the choice to self-administer heroin. Conclusions These findings show that heroin addiction, like addiction to other drugs of abuse, is associated with low D2/3 receptor binding and low pre-synaptic dopamine. However, neither of these outcome measures were associated with the choice to self-administer heroin.

Dopamine Response to Psychosocial Stress in Chronic Cannabis Users: A PET Study With [11C]-(+)-PHNO

“…The lack of effect on stress-induced DA release distinguishes chronic cannabis use disorder from alcoholism, stimulant, and heroin dependence, which have all been shown to reduce amphetamine-induced DA release (Martinez et al, 2007;Martinez et al, 2012;Volkow et al, 1993;Volkow et al, 1996). However, our findings of lack of difference in tracer displacement in response to stress are remarkably consistent with a recent study in chronic CU (Urban et al, 2012).…”

“…For example, while 15% and 24% of those who try cocaine and heroin, respectively, develop dependence, only 9% of those who try cannabis develop dependence. Low striatal dopamine (DA) receptor (D 2/3 ) availability and low amphetamine-induced DA release in the ventral striatum have been observed with several substance-use disorders, including alcoholism (Martinez et al, 2005;Volkow et al, 1996), heroin (Martinez et al, 2012), cocaine (Volkow et al, 1993), and methamphetamine (Volkow et al, 2001) use. Less is known about the changes in DA transmission in chronic cannabis use.…”

Obesity, Dopamine, and Reward Behaviors

“…The development of compulsive food ingestion in animals has been related to the development of decreased striatal DA D2 receptor levels in the setting of decreased DA release and elevated reward thresholds (18). These changes are similar to those seen in alcohol and drug abuse which are characterised by decreased DA release, decreased striatal/ventral DA D2 receptor levels, and anhedonia (19)(20)(21)(22)(23)(24)(25). This has led to the concept of obesity being a food addiction (26,27).…”

Dopamine challenge reveals neuroadaptive changes in marijuana abusers

“…PET imaging of brain revealed a more complex pattern of change in dopamine signaling than previously reported for other specific drugs of abuse. D2/D3 dopamine receptor availability, measured with the D2/D3 receptor antagonist [11C]raclopride, was not reduced in marijuana abusers, in contrast to reduced dopamine receptor availability observed in subjects with other specific substance use disorders (11)(12)(13)(14). This conclusion remains tentative, as the age of the marijuana-abusing cohort was considerably younger than drug-abusing subjects previously interrogated for D2 dopamine receptor availability.…”

“…Repeated drug-induced dopamine surges were subsequently shown to engender neuroadaptive changes in brain regions implicated in drug salience, drug reward, motivation, memory, and executive function (7)(8)(9). In humans dependent on alcohol, cocaine, methamphetamine, nicotine, or heroin, adaptation of dopamine signaling is manifest by reduced D2 dopamine receptor availability and blunted dopamine release in cocaine, heroin, and alcohol abusers challenged with a psychostimulant (10)(11)(12)(13)(14). Interrogation of whether marijuana abusers manifest parallel adaptive changes in dopamine signaling has yielded inconsistent results (15).…”