Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects

Abstract

Cocaine blocks the reuptake of dopamine, a neurotransmitter involved in the control of movement, cognition, motivation and reward. This leads to an increase in extracellular dopamine; the reinforcing effect of cocaine is associated with elevated dopamine levels in the nucleus accumbens. But addiction to cocaine involves other effects, such as craving, loss of control and compulsive drug intake; the role of the dopamine system in these effects is less well-understood. We therefore used positron emission tomography (PET) to compare the responses of cocaine addicts and normal controls to intravenous methylphenidate, a drug that, like cocaine, causes an increase in synaptic dopamine. Addicts showed reduced dopamine release in the striatum, the brain region where the nucleus accumbens is located, and also had a reduced 'high' relative to controls. In contrast, addicts showed an increased response to methylphenidate in the thalamus (a region that conveys sensory input to the cortex). This thalamic response was associated with cocaine craving and was not seen in control subjects. Thus, our findings challenge the notion that addiction involves an enhanced striatal dopamine response to cocaine and/or an enhanced induction of euphoria. Moreover, they suggest a participation of thalamic dopamine pathways in cocaine addiction, a possibility that merits further investigation.

Profiles of Cognitive Dysfunction in Chronic Amphetamine and Heroin Abusers

“…This conclusion is supported by the work of Volkow et al (1997) on the response to stimulants such as methylphenidate in cocaine abusers, as well as by other work suggesting significant cerebral hypoperfusion in the periventricular, frontal and other neocortical regions following cocaine abuse (e.g., Strickland et al 1993).…”

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

“…There are multiple lines of evidence that cocaine dependence is associated with a decrease in D 2 receptor binding [164-167], a pattern that seems to persist after disease remission [165]. Decreases in D 2 receptor binding have also been found in heroin addiction [168], alcohol dependence [169,170], methamphetamine abuse [171,172], prompting a number of researchers to posit that low D 2 receptor availability may serve as a biomarker for substance abuse, potentially reflecting an altered sensitivity to various rewards [173-175].…”

SPECT imaging of D2 dopamine receptors and endogenous dopamine release in mice

“…The D2R has been implicated in cocaine addiction, as well as cocaine craving, in humans [19][20][21][22]. Therefore, the D2R may provide a target for prevention of relapse after cocaine detoxification, and the study of striatal D2R availability in mouse models of cocaine addiction is important to unravel its role in human cocaine addiction.…”