In-vivo quantification of dose-dependent dopamine transporter blockade in the rat striatum with small animal SPECT.

Full Abstract

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.

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Author information

Author/s: Nikolaus, Susanne (S); Antke, Christina (C); Beu, Markus (M); Kley, Konstantin (K); Larisch, Rolf (R); Wirrwar, Andreas (A); Müller, Hans-Wilhelm (HW);

Affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany. Susanne.Nikolaus(-atsign-)uni-duesseldorf.de

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Nuclear medicine communications (Nucl Med Commun), published in England. (Language: eng)

Reference: 2007-Mar; vol 28 (issue 3) : pp 207-13

Dates: Created 2007/01/31; Completed 2007/04/02;

PMID: 17264780, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Algorithms
Animals
Cerebellum - blood supply; radionuclide imaging
Cerebrovascular Circulation - physiology
Data Interpretation, Statistical
Dopamine Plasma Membrane Transport Proteins - antagonists & inhibitors
Dopamine Uptake Inhibitors - pharmacology
Dose-Response Relationship, Drug
Harderian Gland - radionuclide imaging
Male

Male
Methylphenidate - pharmacology
Neck - blood supply
Neostriatum - drug effects; metabolism; radionuclide imaging
Radiopharmaceuticals - diagnostic use
Rats
Rats, Wistar
Salivary Glands - radionuclide imaging
Tomography, Emission-Computed, Single-Photon - methods
Tropanes - diagnostic use

Associated Chemicals: Dopamine Plasma Membrane Transport Proteins (0) ; Dopamine Uptake Inhibitors (0) ; Radiopharmaceuticals (0) ; Tropanes (0) ; Methylphenidate (113-45-1) ; 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane (155797-99-2)

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