Mapping the amphetamine-evoked changes in [11C]raclopride binding in living rat using small animal PET: modulation by MAO-inhibition.
The performance of small animal PET for neuroreceptor studies in a psychopharmacological challenge paradigm is not yet well-described. Therefore, we used microPET and [(11)C]raclopride to map the availability of dopamine D(2/3) receptors in brain of anesthetized rats, first in a baseline condition, and again after challenge with saline or d-amphetamine. Parametric maps of the specific binding (binding potential, pB) were calculated using a reference tissue input from cerebellum, and spatially normalized to a digitized stereotaxic coordinate system for rat brain. In volumes of interest (VOIs), the mean baseline pB (n=6) was 2.05 in dorsal striatum (caudate-putamen), and 1.34 in ventral striatum (nucleus accumbens), and did not significantly differ upon retest 2 h later. The availability of [(11)C]raclopride binding sites at baseline was 8% higher in the right striatum. Challenge with amphetamine sulfate (1 mg/kg, i.v., n=4) decreased pB by 19% in both ventral and dorsal striatum. We have earlier predicted that blockade of monoamine oxidase (MAO) should potentiate the amphetamine-evoked dopamine release, thus enhancing the displacement of [(11)C]raclopride binding in vivo. However, pretreatment of rats with pargyline hydrochloride (4 mg/kg, n=4; 20 mg/kg, n=4) 1 day prior to PET did not potentiate the amphetamine-evoked reduction in dopamine receptor availability within the extended striatum. We conclude that small animal PET can be used to investigate stimulant-induced dopamine release, but that the spatial resolution is insufficient to detect differences between relative changes in dorsal vs. ventral divisions of the rat striatum. Furthermore, the present results do not reveal potentiation of the amphetamine-evoked release of dopamine in rats with MAO inhibition.
Pedersen
Kasper
K
Centre for Functionally Integrative Neuroscience, Aarhus University, Denmark.
Simonsen
Mette
M
Østergaard
Søren D
SD
Munk
Ole Lajord
OL
Rosa-Neto
Pedro
P
Olsen
Aage Kristian
AK
Jensen
Svend Borup
SB
Møller
Arne
A
Cumming
Paul
P
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry / Q000187:drug effects*; D001931:Brain Mapping; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D007839:Functional Laterality / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D017072:Neostriatum / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000493:pharmacokinetics*; D051381:Rats; D011917:Rats, Inbred Lew
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D008996:Monoamine Oxidase Inhibitors; D020891:Raclopride; D010293:Pargyline; D000661:Amphetamine