Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys

Johnson, Amy; Banks, Matthew L.; Blough, Bruce E.; Lile, Joshua A.; Nicholson, Katherine L.; Negus, S. Stevens

doi:10.1016/j.drugalcdep.2016.05.021

Cited by 25 publications

(35 citation statements)

References 44 publications

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“…This lack of coordination across research specialties is a widely recognized problem in clinical and translational science that the National Institutes of Health is addressing by promoting interdisciplinary research teams (e.g., Zerhouni, 2003). Recent efforts to more closely link animal and human laboratory research on cocaine have been undertaken (Foltin et al, 2015), and the authors of this report and the companion article published in this issue (Johnson et al, 2016) sought to extend that work by establishing a collaboration to develop a direct animal-to-human pipeline using similar cocaine self-administration procedures for more efficient evaluation of potential medications for cocaine use disorder.…”

Section: Introductionmentioning

confidence: 99%

Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans

Lile

Stoops

Rush

et al. 2016

Drug and Alcohol Dependence

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Background A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. Methods Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30 mg/70 kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. Results The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. Conclusions These coordinated studies successfully established drug vs. non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use.

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Section: Introductionmentioning

confidence: 99%

Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans

Lile

Stoops

Rush

et al. 2016

Drug and Alcohol Dependence

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“…Major medications used in the treatment of ADHD are dopamine re-uptake inhibitors or psychostimulants (e.g., methyphenidate and mixed amphetamine salts), which also have abuse potential [32,63]. Appropriate medical use of these compounds may be effective in the management of specific stimulant use disorders [4,64]. …”

Section: Scientific Rationale For the Main Approaches Consideredmentioning

confidence: 99%

“…Optimized candidates from these efforts can then undergo Phase I and clinical laboratory studies, to examine the impact of the candidate medication on rewarding, subjective or other effects of specific drugs of abuse [109,172]. When favorable conditions are met, this may be followed by Phase II and III clinical trials of the therapeutic effect of these medications [2,4]. …”

Section: Competitive Environmentmentioning

confidence: 99%

“…It has been argued recently that a number of candidate medications for SUD in the past have not undergone a robust preclinical evaluation (for example in rodent and primate translational models), and that greater integration among preclinical and clinical methodologies should be prioritized [2,4]. In some cases, predictive validity of preclinical and Phase I studies may be compromised due to sub-optimal pharmacological and behavioral designs, which do not model important aspects of the clinical course of the SUD.…”

Section: Competitive Environmentmentioning

confidence: 99%

“…Recent papers have emphasized the importance of optimizing translation between preclinical and clinical development for SUD, and also translation from clinical laboratory studies to Phase II and III trials [2,4,175,176]. These challenges in the development of novel medications for SUD have been recognized in the CNS field as a whole [177,178].…”

Section: Expert Opinionmentioning

confidence: 99%

See 2 more Smart Citations

Medications for substance use disorders (SUD): emerging approaches

Butelman

Kreek

2017

Expert Opinion on Emerging Drugs

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Introduction: Substance use disorders are a group of chronic relapsing disorders of the brain, which have massive public health and societal impact. In some disorders (e.g., heroin / prescription opioid addictions) approved medications have a major long-term benefit. For other substances (e.g., cocaine, amphetamines and cannabis) there are no approved medications, and for alcohol there are approved treatments, which are not in wide usage. Approved treatments for tobacco use disorders are available, and novel medications are also under study. Areas covered: Medication-based approaches which are in advanced preclinical stages, or which have reached proof-of concept clinical laboratory studies, as well as clinical trials. Expert opinion: Current challenges involve optimizing translation between preclinical and clinical development, and between clinical laboratory studies to therapeutic clinical trials. Comorbidities including depression or anxiety are challenges for study design and analysis. Improved pharmacogenomics, biomarker and phenotyping approaches are areas of interest. Pharmacological mechanisms currently under investigation include modulation of glutamatergic, GABA, vasopressin and κ-receptor function, as well as inhibition of monoamine re-uptake. Other factors that affect potential market size for emerging medications include stigma, availability of treatment settings, adoption by clinicians, and the prevalence of persons with SUD who are not actively treatment-seeking.

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Contextual extinction of drug‐associated discriminative stimuli fails to attenuate drug‐vs‐food choice in rhesus monkeys

Banks

Hutsell

Negus

2022

J Exper Analysis Behavior

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Relapse within the context of a substance use disorder can be triggered by cues that function as discriminative stimuli to signal contingencies of drug availability and promote drug‐taking behavior. Extinction procedures can weaken this association between drug‐associated cues and drug‐taking behavior and may reduce the probability of relapse. This study evaluated a regimen of extinction training on cocaine and heroin self‐administration in rhesus monkeys under a drug‐vs‐food choice procedure. Behavior was initially maintained under a concurrent schedule of food (1‐g food pellets; fixed‐ratio 100 schedule) and cocaine injections (0–0.1 mg/kg/injection; fixed‐ratio 10) (n = 4 males) or heroin injections (0–0.01 mg/kg/injection; fixed‐ratio 10) (n = 3 females and 1 male) during daily 2‐hr choice sessions. Subsequently, choice sessions were supplemented by daily 20‐hr saline self‐administration sessions for 14 consecutive days. During saline self‐administration sessions, only drug‐associated discriminative stimuli were presented and responding produced saline injections. Drug continued to be available during choice sessions. Prior to extinction training, both cocaine and heroin maintained dose‐dependent increases in drug‐vs‐food choice. Exposure to 14 saline self‐administration sessions failed to significantly decrease drug choice and increase food choice. These preclinical results do not support the effectiveness of extinguishing drug‐associated discriminative stimuli as a nonpharmacological treatment strategy for reducing drug choice.

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Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys

Cited by 25 publications

References 44 publications

Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans

Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans

Medications for substance use disorders (SUD): emerging approaches

Contextual extinction of drug‐associated discriminative stimuli fails to attenuate drug‐vs‐food choice in rhesus monkeys

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