Dopamine D1 receptor protein is elevated in nucleus accumbens of human, chronic methamphetamine users

Worsley, Julian; Moszczynska, Anna; Falardeau, Pierre; Kalasinsky, Kathryn S.; Schmunk, Gregory A.; Guttman, Mark; Furukawa, Yoshiaki; Ang, Lee Cyn; Adams, Vernard I.; Reiber, Gregory D.; Anthony, Ryan; Wickham, Dennis J.; Kish, Stephen J.

doi:10.1038/sj.mp.4000760

Cited by 74 publications

(59 citation statements)

References 46 publications

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“…Several recent reports have indicated that amphetamine alters dopamine receptor expression in adult humans, animals or cell cultures [Worsley et al, 2000;Tong et al, 2003]. These data provide additional support for the hypothesis that overactivity of the DRD1 system might underlie some of the features of dependence on psychostimulant drugs.…”

supporting

confidence: 69%

“…These reports, taken together with the demonstration that DRD1 agonists can prevent relapse to drug-seeking behavior in rodent [Self et al, 1996] have provided an experimental platform for the selec-tion of the DRD1 as a clinical target for therapeutic intervention in human drug users. In a recent human study, protein levels of DRD1 in the brain of chronic METH users were selectively increased in the NAc [Worsley et al, 2000].…”

Section: Drd1 Upregulationmentioning

confidence: 99%

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Amphetamine-Induced Changes in Dopamine Receptors in Early Postnatal Rat Brain

et al. 2009

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Amphetamines are among the most widely abused drugs. The user population includes a large proportion of women of child-bearing age. The early ontogeny of the axons in the neocortex and other neural structures positions them to influence the development and connectivity of non-aminergic dendrites and axons in these structures. A cascade of abnormalities in neural circuitry may result from the effects of amphetamines on the dopaminergic system. An attempt has been made to investigate the possible changes in the dopaminergic system in neonatal rats (a human third trimester equivalent model) following chronic D-amphetamine exposure. Neonatal rats were administered 5–15 mg/kg D-amphetamine subcutaneously daily from postnatal day 4 to day 10. Several parameters related to the dopaminergic system were measured. The results showed that tyrosine hydroxylase enzyme levels were significantly decreased in the prefrontal cortex, dorsal striatum and nucleus accumbens. Dopamine D1 receptor (DRD1) levels increased in the dorsal striatum whereas dopamine D2 receptor (DRD2) levels significantly decreased in both the prefrontal cortex and the dorsal striatum but significantly increased in the nucleus accumbens. In order to investigate whether these changes occurred at the transcriptional level, DRD1 and DRD2 mRNAs were detected. The results showed that DRD1 mRNA levels were significantly increased in the dorsal striatum whereas DRD2 mRNA levels were significantly increased in all three brain regions. These results indicate that early D-amphetamine exposure altered the dopaminergic system in the developing rat brain. This change may lead to abnormal perinatal stimulation that may yield long-term consequences.

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supporting

confidence: 69%

Section: Drd1 Upregulationmentioning

confidence: 99%

Amphetamine-Induced Changes in Dopamine Receptors in Early Postnatal Rat Brain

et al. 2009

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“…However, the few human studies that have assessed DA D2 receptors in METH abusers have not shown marked decreases in these parameters. For example, in [ 11 C]raclopride-PET studies, decreases in DA D2 receptor availability of only 10% in putamen and 16% in caudate were measured (Volkow et al, 2001) while a post-mortem study showed a trend of 25% decreases in D2 receptor protein levels (Worsley et al, 2000). The range of cumulative METH exposure patterns for those individuals may have contributed to the variability of those measures.…”

Section: Brain Alterationsmentioning

confidence: 99%

Long-Term Methamphetamine Administration in the Vervet Monkey Models Aspects of a Human Exposure: Brain Neurotoxicity and Behavioral Profiles

Melega

Jorgensen

Laćan

et al. 2007

Neuropsychopharmacol

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Methamphetamine (METH)-associated alterations in the human striatal dopamine (DA) system have been identified with positron emission tomography (PET) imaging and post-mortem studies but have not been well correlated with behavioral changes or cumulative METH intake. Animal studies that model some aspects of human long-term METH abuse can establish dose-dependency profiles of both behavioral changes and potential brain neurotoxicities for identifying consequences of particular cumulative exposures. Based on parameters from human and our monkey pharmacokinetic studies, we modeled a prevalent human METH exposure of daily multiple doses in socially housed vervet monkeys. METH doses were escalated over 33 weeks, with final dosages resulting in estimated peak plasma METH concentrations of 1-3 mM, a range measured in human abusers. With larger METH doses, progressive increases in abnormal behavior and decreases in social behavior were observed on 'injection' days. Anxiety increased on 'no injection' days while aggression decreased throughout the study. Thereafter, during 3 weeks abstinence, differences in baseline vs post-METH behaviors were not observed. Post-mortem analysis of METH brains showed 20% lower striatal DA content while autoradiography studies of precommissural striatum showed 35% lower [ 3 H]WIN35428 binding to the DA transporter. No statistically significant changes were detected for [ 3 H]dihydrotetrabenazine binding to the vesicular monoamine transporter (METH-lower by 10%) or for [ 3 H]SCH 23390 and [ 3 H]raclopride binding to DA D1 and D2 receptors, respectively. Collectively, this long-term, escalating dose METH exposure modeling a human abuse pattern, not associated with high-dose binges, resulted in dose-dependent behavioral effects and caused persistent changes in presynaptic striatal DA system integrity.

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“…In addition, an animal's level of sucrose preference can predict its desire to self-administer cocaine (Levine et al, 2003), and sweets will reduce cocaine's reinforcing value (Comer, Lac, Wyvell, & Carroll, 1996), suggesting a relation between sweet taste and drug reward. Both obese rats and chronic drug users have low basal dopamine levels (Hamdi, Porter, & Prasad, 1992), experience periodic exaggerated dopamine release associated with either food (Fetissov et al, 2002) or drug intake (Worsley et al, 2000), and have reduced dopamine D2 receptor and increased D1 receptor expression (Fetissov et al, 2002). A number of addictive behaviors (alcoholism; cocaine, heroin, marijuana, and nicotine use; and glucose bingeing) have been associated with low expression or dysfunction of D2 receptors (Comings & Blum, 2000).…”

Section: Common Neurobiological Substrates For Obesity and Drug Addicmentioning

confidence: 99%

Food reinforcement and eating: A multilevel analysis.

Epstein¹,

Leddy²,

Temple³

et al. 2007

Psychological Bulletin

319

323

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Eating represents a choice among many alternative behaviors. The purpose of this review is to provide an overview of how food reinforcement and behavioral choice theory are related to eating and to show how this theoretical approach may help organize research on eating from molecular genetics through treatment and prevention of obesity. Special emphasis is placed on how food reinforcement and behavioral choice theory are relevant to understanding excess energy intake and obesity and how they provide a framework for examining factors that may influence eating and are outside of those that may regulate energy homeostasis. Methods to measure food reinforcement are reviewed, along with factors that influence the reinforcing value of eating. Contributions of neuroscience and genetics to the study of food reinforcement are illustrated by using the example of dopamine. Implications of food reinforcement for obesity and positive energy balance are explored, with suggestions for novel approaches to obesity treatment based on the synthesis of behavioral and pharmacological approaches to food reinforcement. Keywords food reinforcement; food intake; choice; dopamine; behavioral genetics Choice is ubiquitous. There are many choices that people make that influence their eating and body weight, beginning with how early to get up, to exercise before breakfast or to sleep in, what to have for breakfast, and so on. These choices are made in the context of alternatives, many of which are pleasurable and exert considerable influence to do these behaviors rather than others. The morning is a good time for many people to choose to exercise, but a warm bed and a little extra sleep time represent a powerful alternative that even the most enthusiastic exerciser confronts and often succumbs to. Similarly, eating a good breakfast starts the day off right, but a pastry and coffee may be particularly inviting alternative foods that taste very good and may tempt many away from healthy cereal and fruit. This article provides a theoretical framework for understanding motivation to eat, how people make choices about eating versus engaging in other behaviors, and how these theoretical approaches can provide insights into obesity, mechanisms that regulate food choice, and implications of choice theory for interventions. One of the unique aspects of food reinforcement and behavioral theories of

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Dopamine D1 receptor protein is elevated in nucleus accumbens of human, chronic methamphetamine users

Cited by 74 publications

References 46 publications

Amphetamine-Induced Changes in Dopamine Receptors in Early Postnatal Rat Brain

Amphetamine-Induced Changes in Dopamine Receptors in Early Postnatal Rat Brain

Long-Term Methamphetamine Administration in the Vervet Monkey Models Aspects of a Human Exposure: Brain Neurotoxicity and Behavioral Profiles

Food reinforcement and eating: A multilevel analysis.

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