Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys

Czoty, Paul W.; Gage, H. Donald; Garg, Pradeep; Garg, Sudha; Nader, Michael A.

doi:10.1007/s00213-013-3274-7

Cited by 5 publications

(10 citation statements)

References 51 publications

(57 reference statements)

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“…With regard to partial agonists, a recent PET imaging study in cynomolgus monkeys found that chronic aripiprazole, a D2R partial agonist, produced different effects on D2R binding potential: it appeared to increase binding when the subject had, on average, low D2R availability and decreased binding potential in monkeys with higher average D2R availability. 160 Thus, depending on the long-term consequences of cocaine or METH abuse on receptor availability, the effects of receptor partial agonists may be different than antagonists. There are behavioral nuances as well.…”

Section: Discussionmentioning

confidence: 99%

Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis

et al. 2015

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The dopamine D3 receptor (D3R) is a target for developing medications to treat substance use disorders. D3R-selective compounds with high affinity and varying efficacies have been discovered, providing critical research tools for cell-based studies that have been translated to in vivo models of drug abuse. D3R antagonists and partial agonists have shown especially promising results in rodent models of relapse-like behavior, including stress-, drug-, and cue-induced reinstatement of drug seeking. However, to date, translation to human studies has been limited. Herein, we present an overview and illustrate some of the pitfalls and challenges of developing novel D3R-selective compounds toward clinical utility, especially for treatment of cocaine abuse. Future research and development of D3R-selective antagonists and partial agonists for substance abuse remains critically important but will also require further evaluation and development of translational animal models to determine the best time in the addiction cycle to target D3Rs for optimal therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis

et al. 2015

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“…Briefly, the animals were sedated with 10-15 mg/kg ketamine and transported to the MRI Center where anesthesia was maintained via inhaled 1.5-3% isoflurane (Czoty and Nader 2015; Czoty et al 2013; Czoty and Nader 2012). The animals were artificially ventilated to control physiological parameters across animals.…”

Section: Methodsmentioning

confidence: 99%

Multi-Atlas Library for Eliminating Normalization Failures in Non-Human Primates

et al. 2015

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Introduction Current tools for automated skull stripping, normalization, and segmentation of non-human primate (NHP) brain MRI studies typically demonstrate high failure rates. Many of these failures are due to a poor initial estimate for the affine component of the transformation. The purpose of this study is to introduce a multi-atlas approach to overcome these limitations and drive the failure rate to near zero. Materials and Methods A library of study-specific templates (SST) spanning three Old World primate species (Macaca fascicularis, M. mulatta, Chlorocebus aethiops) was created using a previously described unbiased automated approach. Several modifications were introduced to the methodology to improve initial affine estimation at the study-specific template level, and at the individual subject level. These involve performing multiple separate normalizations to a multi-atlas library of templates and selecting the best performing template on the basis of a covariance similarity metric. This template was then used as an initialization for the affine component of subsequent skull stripping and normalization procedures. Normalization failure rate for SST generation and individual-subject segmentation on a set of 150 NHP was evaluated on the basis of visual inspection. Results The previous automated template creation procedure results in excellent skull stripping, segmentation, and atlas labeling across species. Failure rate at the individual-subject level was approximately 1%, however at the SST generation level it was 17%. Using the new multi-atlas approach, failure rate was further reduced to zero for both SST generation and individual subject processing. Conclusions We describe a multi-atlas library registration approach for driving normalization failures in NHP to zero. It is straightforward to implement, and can have application to a wide variety of existing tools, as well as in difficult populations including neonates and the elderly. This approach is also an important step towards developing fully automated high-throughput processing pipelines that are critical for future high volume multi-center NHP imaging studies for studies of drug abuse and brain health.

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“…The dopamine partial agonist aripiprazole is thought to down-regulate dopamine D2 receptor activity. We believe that this action results in improved brain function (Czoty et al, 2013) and may aid the psychotherapeutic process. Most patients were initially admitted to inpatient level of care before transition to PHP.…”

Section: Discussionmentioning

confidence: 98%

“…Those thresholds were chosen to ensure low weight individuals and allow any prescription of aripiprazole time to affect brain neurotransmitters (Czoty, Gage, Garg, Garg, & Nader, 2013). Furthermore, charts was inspected for diagnoses of major depressive or anxiety disorders that were supported by description of quality and number of symptoms to warrant diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (American Psychiatric Association., 2013).…”

Section: Methodsmentioning

confidence: 99%

“…We requested approval from the Colorado Multiple Institutional Chart selection was further limited to individuals who were admitted at 10th BMI percentile and who were in the treatment program for at least 21 days. Those thresholds were chosen to ensure low weight individuals and allow any prescription of aripiprazole time to affect brain neurotransmitters (Czoty, Gage, Garg, Garg, & Nader, 2013…”

Section: E T H O D Smentioning

confidence: 99%

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The partial dopamine D2 receptor agonist aripiprazole is associated with weight gain in adolescent anorexia nervosa

Frank

Shott

Hagman

et al. 2017

Intl J Eating Disorders

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Objective Finding medication to support treatment of anorexia nervosa has been difficult. Neuroscience based approaches may help in this effort. Recent brain imaging studies in adults and adolescents with anorexia nervosa suggest that dopamine related reward circuits are hypersensitive and could provide a treatment target. Method Here we present a retrospective chart review of 106 adolescents with anorexia nervosa some of whom were treated with the dopamine D2 receptor partial agonist aripiprazole during treatment in a specialized eating disorder program. Results The results show that aripiprazole treatment was associated with greater increase in body mass index (BMI) during treatment. Discussion The use of dopamine receptor agonists may support treatment success in anorexia nervosa and should be further investigated.

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Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys

Cited by 5 publications

References 51 publications

Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis

Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis

Multi-Atlas Library for Eliminating Normalization Failures in Non-Human Primates

The partial dopamine D2 receptor agonist aripiprazole is associated with weight gain in adolescent anorexia nervosa

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