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Wednesday, February 9, 2011

Imaging of alcohol-induced dopamine release in rats: Preliminary findings with [11C]raclopride PET



Microdialysis studies report that systemic alcohol increases extracellular dopamine in the rat striatum. 

The present study examined whether changes in striatal dopamine could be detected in rats using small animal positron emission tomography (PET). 

PET images were acquired in 44 alcohol-naïve male Wistar and alcohol-preferring (P) rats. Subjects received up to three [11C]raclopride scans (rest, alcohol, and saline). Animals were anesthetized with isoflurane and secured on a stereotactic-like holder during all scans. Blood samples were collected from the tail or lateral saphenous vein of 12 animals 10 minutes after tracer injection for determination of blood alcohol concentration (BAC). Time activity curves were extracted from the striatum and the cerebellum and binding potential (BPND) was calculated as a measure of D2 receptor availability. 

Wistars given 1.0g/kg alcohol (20%v/v) I.V. or 3.0g/kg alcohol (20%v/v) I.P showed significant alcohol-induced decreases in BPND.
 
In P rats (given 1.5, 2.25, or 3.0 g/kg alcohol), no individual group showed a statistical effect of alcohol on BPND, but taken together, all P rats receiving I.P. alcohol had significantly lower BPND than rest or saline scans. 

Large decreases in BPND were primarily observed in rats with BAC above 200 mg%. Also, a significant difference was found between baseline BPND of Wistars who had undergone jugular catheterization surgery for I.V. alcohol administration and those who had not. 

These preliminary results suggest that alcohol-induced DA release in the rat striatum is detectable using small animal PET given sufficiently large cohorts and adequate blood alcohol levels.




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