Detection of alcohol-induced dopamine release in alcohol-preferring (P) rats using 11C-raclopride and PET

Objectives Microdialysis has been used to demonstrate that ethanol produces an increase in extracellular dopamine (DA) in the striatum of rats (Heidbreder & De Witte, 1993). The present study examined whether or not similar changes in striatal DA can be detected in P rats using small animal PET.

Methods PET images were acquired from 8 alcohol-naïve male P rats. Rats received three 11C-raclopride scans (at rest, following alcohol, following saline). Scans were performed on IndyPETIII (approx. 1 mm FWHM in-plane). Prior to each scan, rats were anesthetized with 5% isoflurane, secured on a stereotaxic holder, and maintained on 1.5% isoflurane during the scan. P rats received 2.25 g ethanol/kg BW (15% v/v, IP) 5 minutes before tracer injection. Blood samples were collected from the lateral saphenous vein (n=7) 10 min after tracer injection to determine blood alcohol content (BAC) which was 197 mg% ± 26mg% (mean ± SEM). Time activity curves were extracted from striatum and cerebellum and binding potentials (BP) were calculated by a Logan reference technique (Ichise, 2002; Logan, 1996).

Results Alcohol decreased BP by 6.6 ± 6.6% (n=8, p<0.35) whereas saline decreased BP by only 0.72% ± 7.3% (n=8, p<0.83). BAC was positively correlated with decreased BP (r=0.78, p<0.04). Large decreases in BP were observed only in rats with BACs above 200 mg%.

Conclusions Alcohol-induced DA release may be detectable in the striatum of P rats via small animal PET, but a BAC of 200mg% or greater is likely needed in order to induce a significant release of DA in the striatum.

Research Support P60 AA007611-16