Nonhuman primate neuroimaging and the neurobiology of psychostimulant addiction.
Neuroimaging techniques have led to significant advances in our understanding of the neurobiology and treatment of drug addiction in humans. The capability to conduct parallel studies in nonhuman primates and human subjects provides a powerful translational approach to link findings in human and animal research. A significant advantage of nonhuman primate models is the ability to use drug-naïve subjects in longitudinal designs that document the neurobiological changes that are associated with chronic drug use. Moreover, experimental therapeutics can be evaluated in subjects with well-documented histories of drug exposure. The in vivo distribution and pharmacokinetics of drug binding in brain have been related to the time-course of behavioral effects associated with the addictive properties of stimulants. Importantly, the characterization of drug interactions with specific protein targets in brain has identified potential targets for medication development. Neuroimaging has proven especially useful in studying the dynamic changes in neuronal function that may be associated with environmental variables. Last, neuroimaging has been used effectively in nonhuman primates to characterize both transient and long-lasting changes in brain chemistry associated with chronic drug exposure. Although there is some evidence to suggest neurotoxicity in humans with long histories of stimulant use, parallel studies in nonhuman primates have not identified consistent long-term changes in such neurochemical markers. Collectively, the results of these studies of nonhuman primates have enhanced our understanding of the neurobiological basis of stimulant addiction and should have a significant impact on efforts to develop medications to treat stimulant abuse.
Howell
Leonard L
LL
Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. leonard@rmy.emory.edu
Murnane
Kevin S
KS
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics / Q000633:toxicity*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D019788:Fluorodeoxyglucose F18; D000882:Haplorhini; D006801:Humans; D008279:Magnetic Resonance Imaging; D010100:Oxygen / Q000097:blood; D010104:Oxygen Radioisotopes / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011323:Primates / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity; D019966:Substance-Related Disorders / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D027981:Symporters / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D002250:Carbon Radioisotopes; D000697:Central Nervous System Stimulants; D010104:Oxygen Radioisotopes; D017448:Receptors, Dopamine D2; D027981:Symporters; D019788:Fluorodeoxyglucose F18; D010100:Oxygen