In-vivo quantification of dose-dependent dopamine transporter blockade in the rat striatum with small animal SPECT.
OBJECTIVE
This study investigated dopamine transporter blockade in the rat striatum after treatment with various doses of methylphenidate using a high-resolution small animal SPECT ('TierSPECT') and I-FP-CIT.


METHODS
I-FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (3 mg.kg, 10 mg.kg) or vehicle. Rats underwent scanning 2 h after radioligand application. From the spatial resolution of the imaging system and the size of the rat striatum followed that 'true' radioactivity concentrations were underestimated by approximately 50%. From cerebellar and partial volume corrected striatal radioactivity concentrations, striatal equilibrium ratios (V3'') were computed as estimations of the binding potential.


RESULTS
Vehicle-treated animals yielded striatal V3'' values of 3.5+/-0.9 (mean+/-SD). After pre-treatment with 3 mg.kg and 10 mg.kg methylphenidate, striatal V3'' values were reduced to 2.4+/-0.8 (independent t-test, two-tailed, P=0.026) and 1.7+/-0.6 (P<0.001), respectively.


CONCLUSIONS
This first in-vivo study of rat dopamine transporter binding after pre-treatment with various doses of methylphenidate showed a dose-dependent reduction of striatal dopamine transporter binding. Results indicate that in-vivo quantification of dopamine transporter binding is feasible with I-FP-CIT and the TierSPECT method. This may be of future relevance for investigating in-vivo binding properties as well as pharmacological profiles of novel agents acting at the dopamine transporter binding site. Moreover, alterations of striatal transporter densities may be investigated in animal models of neurological and psychiatric diseases such as attention-deficit/hyperactivity disorder and Parkinson's disease.
Nikolaus
Susanne
S
Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany. Susanne.Nikolaus@uni-duesseldorf.de
Antke
Christina
C
Beu
Markus
M
Kley
Konstantin
K
Larisch
Rolf
R
Wirrwar
Andreas
A
Müller
Hans-Wilhelm
HW
D000465:Algorithms; D000818:Animals; D002531:Cerebellum / Q000098:blood supply / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation / Q000502:physiology; D003627:Data Interpretation, Statistical; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006243:Harderian Gland / Q000000981:diagnostic imaging; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D009333:Neck / Q000098:blood supply; D017072:Neostriatum / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D012469:Salivary Glands / Q000000981:diagnostic imaging; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014326:Tropanes
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D019275:Radiopharmaceuticals; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D008774:Methylphenidate