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.
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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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