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Research ArticleJPET Miniseries: Imaging

Nonhuman Primate Positron Emission Tomography Neuroimaging in Drug Abuse Research

Leonard Lee Howell and Kevin Sean Murnane
Journal of Pharmacology and Experimental Therapeutics May 2011, 337 (2) 324-334; DOI: https://doi.org/10.1124/jpet.108.136689
Leonard Lee Howell
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Kevin Sean Murnane
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Abstract

Positron emission tomography (PET) neuroimaging in nonhuman primates has led to significant advances in our current understanding of the neurobiology and treatment of stimulant addiction in humans. PET neuroimaging has defined the in vivo biodistribution and pharmacokinetics of abused drugs and related these findings to the time course of behavioral effects associated with their addictive properties. With novel radiotracers and enhanced resolution, PET neuroimaging techniques have also characterized in vivo drug interactions with specific protein targets in the brain, including neurotransmitter receptors and transporters. In vivo determinations of cerebral blood flow and metabolism have localized brain circuits implicated in the effects of abused drugs and drug-associated stimuli. Moreover, determinations of the predisposing factors to chronic drug use and long-term neurobiological consequences of chronic drug use, such as potential neurotoxicity, have led to novel insights regarding the pathology and treatment of drug addiction. However, similar approaches clearly need to be extended to drug classes other than stimulants. Although dopaminergic systems have been extensively studied, other neurotransmitter systems known to play a critical role in the pharmacological effects of abused drugs have been largely ignored in nonhuman primate PET neuroimaging. Finally, the study of brain activation with PET neuroimaging has been replaced in humans mostly by functional magnetic resonance imaging (fMRI). There has been some success in implementing pharmacological fMRI in awake nonhuman primates. Nevertheless, the unique versatility of PET imaging will continue to complement the systems-level strengths of fMRI, especially in the context of nonhuman primate drug abuse research.

Footnotes

  • This work was funded, in part, by the National Institutes of Health National Institute on Drug Abuse [Grants DA15040 (to K.S.M.), DA10344 (to L.L.H.), DA00517 (to L.L.H.)] and a Yerkes Base Grant [Grant RR00165] (to K.S.M., L.L.H.).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.108.136689.

  • ABBREVIATIONS:

    PET
    positron emission tomography
    fMRI
    functional magnetic resonance imaging
    MDMA
    3,4-methylenedioxymethamphetamine
    DAT
    dopamine transporter
    SERT
    serotonin transporter
    FCP
    fluoroclebopride
    FDG
    fluorodeoxyglucose
    FECNT
    8-(2-fluoroethyl)-2-carbomethoxy-3-(4-chlorophenyl) nortropane
    CFT
    2β-carbomethoxy-3β-(4-fluorophenyl)tropane
    ZIENT
    2β-carbomethoxy-3β-[4′-((Z)-2-iodoethenyl)phenyl]nortropane
    DASB
    3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile
    McN5652
    trans-1,2,3,5,6,10-β-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinolone)
    DTBZ
    (+)-α-dihydrotetrabenazine
    SCH23390
    7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol
    raclopride
    (S)-(−)-3,5-dichloro-N-[(1-ethyl-2-pyrrolidinyl)]methyl-2-hydroxy-6-methoxybenzamide
    fallypride
    (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-fluoropropyl)-2,3-dimethoxybenzamide
    MNPA
    (R)-2-(11)CH(3)O-N-n-propylnorapomorphine
    LY354740
    (2S,4S)-2-amino-4-(4,4-diphenylbut-1-yl)-pentane-1,5-dioic acid
    MPPF
    4-fluoro-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)benzamide
    RTI-113
    phenyl 3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
    RTI-177
    5-[(1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-2-yl]-3-(4-methylphenyl)-1,2-oxazole
    GBR 12909
    1-[2-[bis-(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine
    RTI-112
    (1R,2S,3S)-methyl 3-(4-chloro-3-methylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
    RTI-336
    3β-(4-chlorophenyl)-2β-[3-(4′-methylphenyl)isoxazol-5-yl]tropane hydrochloride
    WIN 35,428
    ((−)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane-1,5-napthalenedisulfonate)
    FLB 457
    (S)-5-bromo-N-[(1-cyclopropylmethyl-2-pyrrolidinyl)methyl]-2,3-dimethoxybenzamide.

  • Received July 21, 2010.
  • Accepted September 9, 2010.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 385 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 385, Issue 1
1 Apr 2023
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Research ArticleJPET Miniseries: Imaging

Nonhuman Primate Positron Emission Tomography Neuroimaging in Drug Abuse Research

Leonard Lee Howell and Kevin Sean Murnane
Journal of Pharmacology and Experimental Therapeutics May 1, 2011, 337 (2) 324-334; DOI: https://doi.org/10.1124/jpet.108.136689

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Research ArticleJPET Miniseries: Imaging

Nonhuman Primate Positron Emission Tomography Neuroimaging in Drug Abuse Research

Leonard Lee Howell and Kevin Sean Murnane
Journal of Pharmacology and Experimental Therapeutics May 1, 2011, 337 (2) 324-334; DOI: https://doi.org/10.1124/jpet.108.136689
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