Functional imaging and neurochemical correlates of stimulant self-administration in primates.

Abstract

Recent advances in neuroimaging and in vivo neurochemistry have documented drug-induced functional changes in brain activity under physiologically relevant conditions. These approaches have significant strengths and important limitations that should be considered. The present review describes current in vivo approaches to characterize drug effects as they relate to behavior, and highlights key contributions derived from each approach in the context of stimulant self-administration in primates. Techniques relating in vitro neurochemistry to behavioral pharmacology are compared to several in vivo approaches, including microdialysis, positron emission tomography (PET) neuroimaging and functional magnetic resonance imaging (fMRI). In vitro neurochemical correlates of behavioral pharmacology established a significant relationship between dopamine and the reinforcing effects of abused stimulants. Subsequent in vivo microdialysis studies in behaving animals supported a critical role for nucleus accumbens dopamine in the reinforcing effects of stimulants. PET neuroimaging in monkeys and humans documented a close relationship between dopamine transporter (DAT) occupancy in vivo and the reinforcing effects of stimulants. The effectiveness of selective DAT inhibitors to reduce cocaine self-administration also was linked to DAT occupancy in vivo. Lastly, the measurement of cerebral blood flow and metabolism with PET and fMRI has begun to define the neuronal circuitry influenced by acute and chronic stimulant exposure. Collectively, in vivo neurochemistry and functional imaging have complemented in vitro approaches and have enhanced our current understanding of the neurobiology of abused stimulants.