Small animal PET for the detection of alcohol- or cocaine-induced striatal dopamine release
Abstract
Objectives. Microdialysis experiments have shown that drugs of abuse, such as alcohol and cocaine, produce an increase in extracellular dopamine (DA) in the striatum. DA release in this part of the brain is believed to mediate the reinforcing properties of alcohol and cocaine that can lead to drug abuse and dependence. Despite the increased use of positron emission tomography (PET) neuroimaging in both humans and animals, there is little to no data on alcohol or cocaine-induced DA release in experimental animals. The present study examined whether or not changes such in striatal DA can be detected in rats using small animal PET. Methods. All scans were performed with 11C-raclopride on the IndyPETIII (∼1mm FWHM in-plane resolution) (Indiana University School of Medicine, Indianapolis). Different aspects of the protocol were varied to examine their effects on imaging the dopaminergic response to drugs of abuse in rats, including the timing of IV cocaine administration, the type and mode of delivery of anesthesia, the strain of rat, and the dose of IP alcohol. Time activity curves were extracted from the striatum and cerebellum (reference region) and binding potentials (BPND) were calculated as a measure of D2 receptor availability. A decrease in BPND was interpreted as an increase in DA (“DA release”). Results. We were able to detect significant decreases in BPND due to alcohol or cocaine administration. Large cohorts are necessary to detect significant changes in both alcohol and cocaine experiments and high blood alcohol levels (>200mg%) may be necessary to maximize detectability of alcohol-induced DA release. No effect of cocaine injection time relative to the injection of raclopride was observed, but differences in BPND were found between isoflurane and ketamine anesthesias.
Degree
M.S.B.M.E.
Advisors
Morris, Purdue University.
Subject Area
Biomedical engineering|Medical imaging|Nuclear physics
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