Nonhuman Primate Positron Emission Tomography Neuroimaging in Drug Abuse Research

Howell, Leonard L.; Murnane, Kevin S.

doi:10.1124/jpet.108.136689

Cited by 28 publications

(20 citation statements)

References 89 publications

(97 reference statements)

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“…Furthermore, their complex social and behavioral repertoire allows for hypothesis-driven, longitudinal studies of disease states (Weerts et al 2007; Kaplan et al 2010). In addition, the ability to study the same subjects for years allows for within-subject assessments of multiple independent variables (Nader et al 2010; Czoty et al 2011; Howell and Murnane 2011; Gould et al 2012). …”

Section: Introductionmentioning

confidence: 99%

Nonhuman primate models of social behavior and cocaine abuse

et al. 2012

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Rationale Although cocaine is often abused in social situations, very few animal studies examine the effects of cocaine in the context of social behavior. Objectives This review highlights studies investigating the behavioral effects of cocaine in the context of social housing conditions using nonhuman primates. In addition, this review presents recent findings examining the effects of self-administering cocaine on social behavior and the effects of manipulations hypothesized to be stressful or enriching on the interactions between cocaine reinforcement and social rank. The following dependent variables are examined: 1) cocaine-induced changes in social behavior and 2) cocaine self-administration in cynomolgus monkeys of varying social ranks. The independent variables examined include several environmental and pharmacological manipulations. Conclusions The studies reviewed here indicate that several variables can differentially affect cocaine self-administration when studied in a social context, rather than in individually housed animals. These variables include the social rank and sex of the individual, drug history, the nature of the “fear”-inducing manipulation, and the reliability of cortisol as an appropriate measure of “stress.” While the inclusion of socially housed animals necessitates larger sample sizes, animal models incorporating social behavior are more homologous to the human condition and should be implemented when possible.

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Section: Introductionmentioning

confidence: 99%

Nonhuman primate models of social behavior and cocaine abuse

et al. 2012

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“…Marmosets may become more prevalent in biomedical research considering ease of handling, lower costs and a favorable reproductive cycle. Both normal NHP imaging, as well as imaging using specific NHP models of neuropathology [201] and drug abuse [204,205] have been described. Due to the limited availability of NHP, a multi-institutional collaboration might be necessary to conduct studies.…”

Section: Preclinical Imagingmentioning

confidence: 99%

Tactics for preclinical validation of receptor-binding radiotracers

Lever

Fan

Lever

2017

Nuclear Medicine and Biology

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Introduction Aspects of radiopharmaceutical development are illustrated through preclinical studies of [125I]-(E)-1-(2-(2,3-dihydrobenzofuran-5-yl)ethyl)-4-(iodoallyl)piperazine ([125I]-E-IA- BF-PE-PIPZE), a radioligand for sigma-1 (σ1) receptors, coupled with examples from the recent literature. Findings are compared to those previously observed for [125I]-(E)-1-(2-(2,3-dimethoxy-5-yl)ethyl)-4-(iodoallyl)piperazine ([125I]-E-IA-DM-PE-PIPZE). Methods Syntheses of E-IA-BF-PE-PIPZE and [125I]-E-IA-BF-PE-PIPZE were accomplished by standard methods. In vitro receptor binding studies and autoradiography were performed, and binding potential was predicted. Measurements of lipophilicity and protein binding were obtained. In vivo studies were conducted in mice to evaluate radioligand stability, as well as specific binding to σ1 sites in brain, brain regions and peripheral organs in the presence and absence of potential blockers. Results E-IA-BF-PE-PIPZE exhibited high affinity and selectivity for σ1 receptors (Ki = 0.43 ± 0.03 nM, σ2 / σ1 = 173). [125I]-E-IA-BF-PE-PIPZE was prepared in good yield and purity, with high specific activity. Radioligand binding provided dissociation (koff) and association (kon) rate constants, along with a measured Kd of 0.24 ± 0.01 nM and Bmax of 472 ± 13 fmol / mg protein. The radioligand proved suitable for quantitative autoradiography in vitro using brain sections. Moderate lipophilicity, Log D7.4 2.69 ± 0.28, was determined, and protein binding was 71 ± 0.3%. In vivo, high initial whole brain uptake, > 6% injected dose / g, cleared slowly over 24 h. Specific binding represented 75% to 93% of total binding from 15 min to 24 h. Findings were confirmed and extended by regional brain biodistribution. Radiometabolites were not observed in brain (1%). Conclusions Substitution of dihydrobenzofuranylethyl for dimethoxyphenethyl increased radioligand affinity for σ1 receptors by 16-fold. While high specific binding to σ1 receptors was observed for both radioligands in vivo, [125I]-E-IA-BF-PE-PIPZE displayed much slower clearance kinetics than [125I]-E-IA-DM-PE-PIPZE. Thus, minor structural modifications of σ1 receptor radioligands lead to major differences in binding properties in vitro and in vivo.

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“…There are several excellent recent reviews involving nonhuman primate imaging studies (Howell and Murnane, 2011; Murnane and Howell, 2011; Gould et al, 2012, 2013). Most of the imaging studies described in this review utilized positron emission tomography (PET), although we do mention other imaging modalities, including those based on magnetic resonance imaging (MRI) (see Nader and Czoty, 2008 for additional imaging rationale for studies involving nonhuman primates).…”

Section: Introductionmentioning

confidence: 99%

Environmental modulation of drug taking: Nonhuman primate models of cocaine abuse and PET neuroimaging

Nader

Banks

2014

Neuropharmacology

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The current review highlights the importance of environmental variables on cocaine self-administration in nonhuman primate models of drug abuse. In addition to describing the behavioral consequences, potential mechanisms of action are discussed, based on imaging results using the non-invasive and translational technique of positron emission tomography (PET). In this review, the role of three environmental variables – both positive and negative - are described: alternative non-drug reinforcers; social rank (as an independent variable) and punishment of cocaine self-administration. These environmental stimuli can profoundly influence brain function and drug self-administration. We focus on environmental manipulations involving non-drug alternatives (e.g., food reinforcement) using choice paradigms. Manipulations such as response cost and social variables (e.g., social rank, social stress) also influence the behavioral effects of drugs. Importantly, these manipulations are amenable to brain imaging studies. Taken together, these studies emphasize the profound impact environmental variables can have on drug taking, which should provide important information related to individual-subject variability in treatment responsiveness, and the imaging work may highlight pharmacological targets for medications related to treating drug abuse.

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Nonhuman Primate Positron Emission Tomography Neuroimaging in Drug Abuse Research

Cited by 28 publications

References 89 publications

Nonhuman primate models of social behavior and cocaine abuse

Nonhuman primate models of social behavior and cocaine abuse

Tactics for preclinical validation of receptor-binding radiotracers

Environmental modulation of drug taking: Nonhuman primate models of cocaine abuse and PET neuroimaging

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