Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later (original) (raw)
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Striatal dopamine (D2) receptor availability predicts socially desirable responding
Neuroimage, 2007
Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [ 11 C]raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals. Synapse 64:397-402,
Synapse, 1993
Decreased dopaminergic function has been postulated to underlie cocaine addiction. To examine the possibility that dysfunction of brain regions subserved by the dopamine system could promote cocaine self-administration, positron emission tomography and a dual-tracer approach was used to examine dopamine D, receptor availability and regional brain glucose metabolism in cocaine abusers. When compared to normal controls, cocaine abusers showed significant decreases in dopamine D, receptor availability which persisted 3-4 months after detoxification. Decreas'es in dopamine D, receptor availability were associated with decreased metabolism in several regions of the frontal lobes, most markedly orbito-frontal cortex and cingulate gyri. Dopamine dysregulation of these brain areas which are involved in the channeling of drive and affect could lead to loss of control resulting in compulsive drug-taking behavior.
Cocaine cue-induced dopamine release in the human prefrontal cortex
Journal of psychiatry & neuroscience : JPN, 2016
Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical ...
Neuropsychopharmacology, 2004
Striatal dopamine D 2 receptors have been implicated in the neurobiology of cocaine addiction. Previous imaging studies showed reduced striatal D 2 receptor availability in chronic cocaine abusers, and animal studies suggested that low D 2 receptor availability promotes cocaine self-administration. Here, D 2 receptor availability was assessed with positron emission tomography (PET) and [ 11 C]raclopride in the limbic, associative, and sensori-motor subdivisions of the striatum in 17 recently detoxified chronic cocaine-dependent (CCD) subjects and 17 matched healthy control (HC) subjects. In addition, the relationship between regional D 2 receptor availability and behavioral measures obtained in cocaine self-administration sessions was investigated in CCD subjects. [ 11 C]Raclopride binding potential was significantly reduced by 15.2% in the limbic striatum, 15.0% in the associative striatum, and 17.1% in the sensori-motor striatum in CCD subjects compared to HC subjects. In CCD subjects, no relationship was detected between D 2 availability in striatal regions and either the positive effects of smoked cocaine or the choice of cocaine over an alternative reinforcer (money) following a priming dose of cocaine (a laboratory model of relapse). Thus, this study confirms previous reports of a modest decrease in D 2 receptor availability in CCD subjects, and establishes that this decrease is generalized throughout the striatum. However, this study failed to demonstrate a relationship between D 2 receptor availability and cocaine-induced cocaine-taking behavior. Additional research is warranted to unravel potential neurobiological traits that might confer vulnerability to relapse in detoxified CCD subjects.
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2015
Background: Individuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D2-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D2/D3 receptor availability is negatively correlated with preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence. Methods: Fifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography (PET) scanning with [(18)F]fallypride. Results: MA users displayed steeper temporal discounting (p = 0.030) and lower striatal D2/D3 re...
Increased Occupancy of Dopamine Receptors in Human Striatum during Cue-Elicited Cocaine Craving
Neuropsychopharmacology, 2007
In all, 19 research subjects, with current histories of frequent cocaine use, were exposed to cocaine-related cues to elicit drug craving. We measured the change of occupancy of dopamine at D2-like receptors with positron emission tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous dopamine release), based on the displacement of radiotracer [ 11 C]raclopride. Receptor occupancy by dopamine increased significantly in putamen of participants who reported cue-elicited craving compared to those who did not. Further, the intensity of craving was positively correlated with the increase in dopamine receptor occupancy in the putamen. These results provide direct evidence that occupancy of dopamine receptors in human dorsal striatum increased in proportion to subjective craving, presumably because of increased release of intrasynaptic dopamine.
American Journal of Psychiatry, 2014
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 [ 11 C]raclopride, before and after the administration of a stimulant (methylphenidate), to measure striatal D 2/3 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.
American Journal of Psychiatry, 2011
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 [ 11 C]raclopride, before and after the administration of a stimulant (methylphenidate), to measure striatal D 2/3 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.
Dopamine in the Brain: Hypothesizing Surfeit or Deficit Links to Reward and Addiction
Journal of Reward Deficiency Syndrome, 2015
Recently there has been debate concerning the role of brain dopamine in reward and addiction. David Nutt and associates eloquently proposed that dopamine (DA) may be central to psycho stimulant dependence and some what important for alcohol, but not important for opiates, nicotine or even cannabis. Others have also argued that surfeit theories can explain for example cocaine seeking behavior as well as non-substance-related addictive behaviors. It seems prudent to distinguish between what constitutes "surfeit" compared to" deficit" in terms of short-term (acute) and long-term (chronic) brain reward circuitry responsivity. In an attempt to resolve controversy regarding the contributions of mesolimbic DA systems to reward, we review the three main competing explanatory categories: "liking", "learning", and "wanting". They are (a) the hedonic impact-liking reward, (b) the ability to predict rewarding effects-learning and (c) the incentive salience of reward-related stimuli-wanting. In terms of acute effects, most of the evidence seems to favor the "surfeit theory". Due to preferential dopamine release at mesolimbic-VTA-caudate-accumbens loci most drugs of abuse and Reward Deficiency Syndrome (RDS) behaviors have been linked to heightened feelings of well-being and hyperdopaminergic states.The "dopamine hypotheses" originally thought to be simple, is now believed to be quite complex and involves encoding the set point of hedonic tone, encoding attention, reward expectancy, and incentive motivation. Importantly, Willuhn et al. shows that in a self-administration paradigm, (chronic) excessive use of cocaine is caused by decreased phasic dopamine signaling in the striatum. In terms of chronic addictions, others have shown a blunted responsivity at brain reward sites with food, nicotine, and even gambling behavior. Finally, we are cognizant of the differences in dopaminergic function as addiction progresses and argue that relapse may be tied to dopamine deficiency. Vulnerability to addiction and relapse may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants and elevated stress levels. We therefore propose that dopamine homeostasis may be a preferred goal to combat relapse.