Effects of chronic cocaine abuse on postsynaptic dopamine receptors

Volkow, Nora D.; Fowler, Joanna S.; Wolf, Alfred P.; Schlyer, David; Shiue, Chyng‐Yann; Alpert, Robert; Dewey, Stephen L.; Logan, Jean; Bendriem, B.; Christman, David R.

doi:10.1176/ajp.147.6.719

Cited by 358 publications

(62 citation statements)

References 22 publications

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“…Non-human primates with low DA D2 receptor density show higher frequency of cocaine self-administration (Nader et al , 2006). The brain tissues of cocaine addicts show reduced D2 receptor availability via PET scan after chronic cocaine addiction (Volkow et al , 1990), and healthy volunteers with lower dopamine D2 receptor density reported liking the effects of methylphenidate (a stimulant with some structural and pharmacologic similarities to cocaine), whereas individuals with higher dopamine D2 receptor density reported more intense unpleasant effects of methylphenidate (Volkow et al , 1999). …”

Section: Discussionmentioning

confidence: 99%

A variant in ANKK1 modulates acute subjective effects of cocaine: a preliminary study

Spellicy

Harding

Hamon

et al. 2014

Genes Brain and Behavior

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This study aimed to evaluate whether functional variants in the ankyrin repeat and kinase domain-containing 1 gene (ANKK1) and/or the dopamine receptor D2 gene (DRD2) modulate the subjective effects (reward or non-reward response to a stimulus) produced by cocaine administration. Cocaine-dependent participants (N = 47) were administered 40 mg of cocaine or placebo at time 0, and a subjective effects questionnaire (visual analog scale) was administered 15 minutes prior to cocaine administration, and at 5, 10,15, and 20 minutes following administration. The influence of polymorphisms in the ANKK1 and DRD2 genes on subjective experience of cocaine in the laboratory was tested. Participants with a T allele of ANKK1 rs1800497 experienced greater subjective ‘high’ (p = 0.00006), ‘any drug effect’ (p = 0.0003), and ‘like’ (p = 0.0004) relative to the CC genotype group. Although the variant in the DRD2 gene was shown to be associated with subjective effects, LD analysis revealed this association was driven by the ANKK1 rs1800497 variant. A participant’s ANKK1 genotype may identify individuals who are likely to experience greater positive subjective effects following cocaine exposure, including greater ‘high’ and ‘like’, and these individuals may have increased vulnerability to continue using cocaine or they may be at greater risk to relapse during periods of abstinence. However, these results are preliminary and replication is necessary to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

A variant in ANKK1 modulates acute subjective effects of cocaine: a preliminary study

Spellicy

Harding

Hamon

et al. 2014

Genes Brain and Behavior

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“…The procedures for subjects positioning and scanning protocols have been described previously [25, 28]. In short, emission scans were started immediately after injection of 4–8 mCi (specific activity 0.5–1.5 Ci/µM at end of bombardment or EOB).…”

Section: Methodsmentioning

confidence: 99%

Socioeconomic status is associated with striatal dopamine D2/D3 receptors in healthy volunteers but not in cocaine abusers

Wiers

Shokri‐Kojori

Cabrera

et al. 2016

Neuroscience Letters

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Positron emission tomography (PET) studies in animals and humans have shown that social status is associated with striatal dopamine D2/D3 receptor (D2/D3R) availability. That is, higher social hierarchy and higher scores on questionnaires assessing social status correlated positively with striatal D2/D3R availability in animals and humans respectively. Furthermore, subordinate monkeys were vulnerable to cocaine self-administration, suggesting that alternations in social hierarchy can change D2/D3R availability and vulnerability to cocaine use. Here, we investigated whether socioeconomic status (SES) measured with the Hollingshead scale is associated with striatal D2D/3R availability using [11C]raclopride PET in 38 cocaine abusers and 42 healthy controls matched for age and education. Compared to controls, cocaine abusers showed lower D2/D3R availability in the caudate, putamen and ventral striatum (all p≤.001). Despite matching groups for education, SES scores were lower in cocaine abusers than controls (p<.001). In the control group only, SES scores significantly correlated with D2/D3R in caudate (r=.35, p=.024) and putamen (r=.39, p=.011) but not in ventral striatum (p=.61); all corrected for age. The study confirms that SES is associated with striatal D2/D3R availability in healthy human volunteers. However, reductions in D2/D3R availability in cocaine abusers may be driven by factors other than SES such as chronic cocaine exposure.

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“…These studies show that subjects with substance use disorders, compared to control subjects, have a decrease in the D 2 receptors in the striatum on the order of about 20%. The first report was in 1990, where a study showed that cocaine abuse was associated with a decrease in D 2 receptor availability in the striatum compared to controls (Volkow et al, 1990), and has been followed by a series of studies confirming this observation (Martinez et al, 2004; Martinez et al, 2011; Martinez et al, 2009; Volkow et al, 1993; Volkow et al, 1997). However, this finding is not isolated to cocaine dependence.…”

Section: Introductionmentioning

confidence: 99%

Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity

Trifilieff

Martínez²

2014

Neuropharmacology

148

112

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Dependence to drugs of abuse is closely associated with impulsivity, or the propensity to choose a lower, but immediate, reward over a delayed, but more valuable outcome. Here, we review clinical and preclinical studies showing that striatal dopamine signaling and D2 receptor levels – which have been shown to be decreased in addiction - directly impact impulsivity, which is itself predictive of drug self-administration. Based on these studies, we propose that the alterations in D2 receptor binding and dopamine release seen in imaging studies of addiction constitute neurobiological markers of impulsivity. Recent studies in animals also show that higher striatal dopamine signaling at the D2 receptor is associated with a greater willingness to expend effort to reach goals, and we propose that this same relationship applies to humans, particularly with respect to recovery from addiction.

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Effects of chronic cocaine abuse on postsynaptic dopamine receptors

Cited by 358 publications

References 22 publications

A variant in ANKK1 modulates acute subjective effects of cocaine: a preliminary study

A variant in ANKK1 modulates acute subjective effects of cocaine: a preliminary study

Socioeconomic status is associated with striatal dopamine D2/D3 receptors in healthy volunteers but not in cocaine abusers

Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity

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