A novel method of imaging dopamine release in awake animals with positron emission tomography (PET)

Abstract

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Objectives: Determine if the neurochemical affects of a behavioral paradigm or various drug challenges could be measured without the confounding influences of anesthesia associated with the imaging of animals using positron emission tomography.

Methods: Control animals(n=8), S.D. Rat, were permitted to move freely for 30 min following intravenous(IV) 11C-raclopride(RAC) admin. Animals were then anesthetized and scanned for 25 min. Separate groups of animals received pharmacological challenges of: unlabeled rac(5mg/kgIV) co-administered with RAC(n=4), methamphetamine(METH,5mg/kg IP,n=5) and S-GVG(150mg/kgIP) followed by METH(n=6) 10 min prior to RAC. Another group(n=5) underwent hand restraint and lifting during the 30 min uptake period of RAC. All challenged groups were anesthetized and scanned for 25 min. following 30min of RAC uptake. Traditional 60 min scans of RAC were performed in animals(n=4) anesthetized for the 30min uptake period. Striatal to cerebellar ratios were calculated for all groups during the last 25 min of scanning.

Results: There was no significant difference between awake freely moving animals vs anesthetized animals. Unlabeled rac produced a ~93% occupancy of D2 receptors in both awake and anesthetized animals. METH administration decreased RAC binding by 35%. S-GVG blocked METH induced increases of dopamine. Animal restraint produced a 39% decrease in RAC binding.

Conclusions: These studies support a novel molecular imaging methodology in which animals receive the imaging agent without anesthesia. During this uptake period animals can be subjected to various behavioral paradigms or pharmacological challenges and then scanned within the tomograph. This provides researchers with increased flexibility in measuring specific molecular events associated with more complex behaviors.

Research Support: NIH DA15041 and DA22346