Imaging Dopamine Transmission in Cocaine Dependence: Link Between Neurochemistry and Response to Treatment

Abstract

Previous research has shown that dopamine signaling in the limbic striatum is crucial for selecting adaptive, motivated behavior, and that disrupted dopamine transmission is associated with impulsive and maladaptive behavior. In humans, Positron Emission Tomography (PET) imaging studies have shown that cocaine dependence is associated with the dysregulation of striatal dopamine signaling, which is associated with cocaine seeking behavior. The goal of the present study was to investigate whether this association applies to the treatment setting. Our hypothesis was that dopamine signaling in the limbic striatum would be associated with response to a behavioral treatment that uses positive reinforcement to replace impulsive cocaine use with constructive personal goals. Prior to treatment, cocaine dependent subjects underwent two PET scans using [11C]raclopride, before and after the administration of a stimulant (methylphenidate), to measure striatal D2/3 receptor binding and pre-synaptic dopamine release. The results showed that both of these outcome measures were reduced in the volunteers who failed to respond to treatment compared to those who experienced a positive treatment response. These findings provide insight into the neurochemistry of treatment response and show that low dopamine transmission is associated with treatment failure. In addition, these data suggest that the combination of behavioral treatment with methods that increase striatal dopamine signaling might serve as a therapeutic strategy for cocaine dependence.

Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment

“…A deficit in striatal D2/D3 dopamine receptor binding is a common feature across substance use disorders (Bonci et al, 2013;Broft and Martinez, 2012). In stimulant dependence, this deficit is linked to treatment success rates (Martinez et al, 2011;Wang et al, 2012) and measures of impulsivity (Lee et al, 2009) and decision making (Ballard et al, 2015). Although these observations suggest that augmenting signaling at D2/D3 receptors may be an effective therapeutic target in substance use disorders, dopamine agonist therapy has shown limited success in improving treatment outcomes for stimulant dependence (Ling et al, 2006).…”

“…Extrastriatal VOIs for the hippocampus, amygdala, and thalamus were defined using the FSL software package and a whole striatum VOI was created by combining VOIs of the caudate, putamen, and nucleus accumbens. The functional subdivisions of the striatum (Martinez et al, 2011) and midbrain (Zald et al, 2010) were defined using published guidelines. The cerebellum was selected as an appropriate reference region (Hall et al, 1994;Ishibashi et al, 2013).…”

In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

“…On the other hand, recently (Rominger et al, 2012) striatal DRD2/3 binding has been reported to increase significantly by 29% between the first day and 1 year of abstinence. Furthermore, it is interesting to note that in a recent [ 11 C]raclopride study by Martinez et al (2011), in cocaine addiction the patients who responded to contingency management treatment and thus remained abstinent did not differ from healthy controls in DRD2/3 levels measured pre-treatment. Similar results in methamphetamine-dependent patients have been reported by Wang et al (2012).…”

Impulsivity as a vulnerability factor for poor addiction treatment outcomes: A review of neurocognitive findings among individuals with substance use disorders

“…Therefore, a more detailed understanding of the (neural) mechanisms underlying the effects of impulsivity on treatment outcomes is needed, as this may lead to novel interventions aimed at minimizing these negative effects and may facilitate treatment responding in these subjects. One neural mechanism potentially linking impulsivity with poor treatment outcomes is a motivational deficit associated with dopamine dysfunction: pronounced disruptions in dopamine functioning associated with impulsivity may produce difficulties in attributing salience to novel reward-indicating stimuli (Beck et al, 2009;Martinez et al, 2011) and affect the ability of the individual to successfully modify behavior in the face of enriched rewarding contingencies (Goto & Grace, 2008). Speculatively, pharmacological interventions aimed at restoring dopamine functioning might facilitate CM-responding in these individuals by targeting neurobiological bottom-up processes associated with reward processing and salience attribution .…”