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

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.

journal_name

Nucl Med Commun

journal_title

Nuclear medicine communications

authors

Nikolaus S,Antke C,Beu M,Kley K,Larisch R,Wirrwar A,Müller HW

doi

10.1097/MNM.0b013e328014a0df

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

207-13

issue

eissn

0143-3636

issn

1473-5628

pii

00006231-200703000-00010

journal_volume

pub_type

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