title: Imaging of alcohol-induced dopamine release in rats:preliminary findings with [(11) C]raclopride PET.
abstract: Microdialysis studies report that systemic alcohol increases extracellular dopamine (DA) in the rat striatum. The present study examined whether changes in striatal DA 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 [(11) C]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 min after tracer injection for determination of blood alcohol concentration (BAC). Time activity curves were extracted from the striatum and the cerebellum and binding potential (BP(ND) ) was calculated as a measure of D(2) receptor availability. Wistars given 1.0 g kg(-1) alcohol (20%v/v) i.v. or 3.0 g kg(-1) alcohol (20%v/v) i.p. showed significant alcohol-induced decreases in BP(ND) . In P rats (given 1.5, 2.25, or 3.0 g kg(-1) alcohol), no individual group showed a statistical effect of alcohol on BP(ND) , but taken together, all P rats receiving i.p. alcohol had significantly lower BP(ND) than rest or saline scans. Large decreases in BP(ND) were primarily observed in rats with BAC above 200 mg%. Also, a significant difference was found between baseline BP(ND) of Wistars who had undergone jugular catheterization surgery for i.v. alcohol administration and those who had not. 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.
authors.affiliation: Department of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Sullivan
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Risacher
authors.forename: Marc D
authors.initials: MD
authors.lastname: Normandin
authors.forename: Karmen K
authors.initials: KK
authors.lastname: Yoder
authors.forename: Janice C
authors.initials: JC
authors.lastname: Froehlich
authors.forename: Evan D
authors.initials: ED
authors.lastname: Morris
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002247:Carbon Isotopes / Q000097:blood / Q000493:pharmacokinetics; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D008297:Male; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D020891:Raclopride / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002247:Carbon Isotopes; D002492:Central Nervous System Depressants; D018492:Dopamine Antagonists; D000431:Ethanol; D020891:Raclopride; D004298:Dopamine