RT Journal Article
SR Electronic
T1 Integrating molecular imaging and behavioral neuroscience: Seeing animal models in a new light
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1200
OP 1200
VO 52
IS supplement 1
A1 Alexandra Aarons
A1 Christina Veith
A1 Joseph Carrion
A1 Sandra Scherrer
A1 Amanda Talan
A1 Stergiani Agorastos
A1 Stephen Dewey
A1 Wynne Schiffer
YR 2011
UL http://jnm.snmjournals.org/content/52/supplement_1/1200.abstract
AB 1200 Objectives Behavioral neuroimaging in animals allows us to map preclinical models of clinical studies by examining both behavioral and molecular imaging endpoints simultaneously. We will describe the development and validation of a new paradigm in which PET and receptor specific radiotracers can capture dynamic molecular events in behaving animals. Our change in emphasis from imaging nonspecific brain targets to specific molecular events represents a significant shift and offers a new tool for understanding brain/behavior relationships. Methods Using [11C]-raclopride (11C-rac) as a prototypical probe whose displacement reflects changing dopamine (DA), we constructed drug challenges to directly perturb 11C-rac (loading doses of cold rac) or indirectly change 11C-rac by changing DA (METH to increase and AMPT to decrease DA). Paired scans were performed where uptake occurred in the awake state followed by anesthesia. Behaviors were videotaped digitally analyzed and compared to changes in 11C-rac binding. Results Behavioral challenges revealed parallels analogous to human PET studies. Stress decreased 11C-rac binding, an effect that significantly correlated with behavior and was similar in magnitude to that following METH. Cue exposure in cocaine-addicted animals significantly decreased 11C-rac; this decrease correlated with measures of craving and the magnitude was similar to the decrease in 11C-rac from acute cocaine. Conclusions We found that changes in 11C-rac binding were closely linked to individual differences in behavior in each model tested. Animals with little genetic variation and no difference in rearing will respond uniquely to stress and this response closely reflects 11C-rac binding. This reflects a variability common to clinical PET studies. Research Support Supported by DOD PR02620 and NIH R01-DA02529 to WKS