title: Mapping the amphetamine-evoked dopamine release in the brain of the Göttingen minipig.
abstract: The availability of dopamine D(2/3) binding sites in brain of six male and six female Göttingen minipigs was measured in a baseline condition and after challenge with amphetamine sulfate (1mg/kg, i.v.) in PET studies with [(11)C]raclopride. Maps of the binding potential (pB; B(max)/K(d)) of [(11)C]raclopride were spatially normalized and co-registered to a common stereotaxic coordinate system for pig brain. The pB maps were then analyzed by volume of interest and voxel-wise comparisons of gender and condition. The mean baseline pB tended to be 10-20% higher in striatum of the female group, but this gender difference was not significant. Variance of the mean baseline pB was higher in the males (44%) than in females (30%), but there was no correlation between pB and individual plasma cortisol or testosterone concentrations. Using statistical parametric mapping, we detected a focus in the right posterior putamen where the magnitude of the amphetamine-evoked decrease in pB was greater in the male than in the female group. Thus, the spatial pattern of reactivity of dopamine D(2/3) receptor availability to amphetamine challenge is not identical in male and female pigs. Within the entire population, the decline in pB evoked by amphetamine (Delta pB) was greater in the ventral striatum (-28%) than in the caudate nucleus (-17%), consistent with earlier reports in monkeys and humans. The magnitude of Delta pB correlated highly with the baseline pB values in all divisions of the striatum. Based upon the principles of competitive binding, the slope of this empirical relationship, f(i), is equal to the fraction of [(11)C]raclopride binding sites sensitive to endogenous dopamine; the magnitude of this fraction ranged from 0.29 in the caudate to 0.36 in the ventral striatum.
authors.affiliation: Department of Psychiatry, University Hospital of Copenhagen, Bispebjerg, Denmark. nml@kvl.dk
authors.forename: Nanna Marie
authors.initials: NM
authors.lastname: Lind
authors.forename: Aage Kristian
authors.initials: AK
authors.lastname: Olsen
authors.forename: Anette
authors.initials: A
authors.lastname: Moustgaard
authors.forename: Svend Borup
authors.initials: SB
authors.lastname: Jensen
authors.forename: Steen
authors.initials: S
authors.lastname: Jakobsen
authors.forename: Axel Kornerup
authors.initials: AK
authors.lastname: Hansen
authors.forename: Sidse Marie
authors.initials: SM
authors.lastname: Arnfred
authors.forename: Ralf Peter
authors.initials: RP
authors.lastname: Hemmingsen
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D020891:Raclopride / Q000493:pharmacokinetics; D012737:Sex Factors; D013552:Swine; D013556:Swine, Miniature
chemical_list: D002247:Carbon Isotopes; D000697:Central Nervous System Stimulants; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine