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Effects of L-DOPA on striatal iodine-123-FP-CIT binding and behavioral parameters in the rat.

Nikolaus S, Beu M, Hautzel H, Silva AM, Antke C, Wirrwar A, Huston JP, Müller HW - Nucl Med Commun (2013)

Bottom Line: Challenge with 5 and 10 mg/kg L-DOPA/benserazide led to mean reductions in DAT binding by 34 and 20%, respectively.Results indicate a biphasic response with a higher effect on DAT after the lower dose of L-DOPA.The reduction in DAT binding may be interpreted in terms of competition between [123I]FP-CIT and endogenous dopamine.

View Article: PubMed Central - PubMed

Affiliation: aClinic of Nuclear Medicine, University Hospital Düsseldorf bCenter for Behavioural Neuroscience, Heinrich-Heine University, Düsseldorf cDepartment of Nuclear Medicine, Helios Clinic Krefeld GmbH, Krefeld, Germany.

ABSTRACT

Purpose: The effect of clinical L-3,4-dihydroxyphenylalanine (L-DOPA) doses on the binding of [121I]N-Ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (121[I]FP-CIT) to the rat dopamine transporter (DAT) was investigated using small animal single-photon emission computed tomography.

Materials and methods: DAT binding was measured at baseline, after challenge with the aromatic L-amino acid decarboxylase inhibitor benserazide, and after challenge with either 5 or 10 mg/kg L-DOPA plus benserazide. For baseline and challenges, striatal equilibrium ratios (V3'') were computed as an estimation of the binding potential. Moreover, striatal V3'' values were correlated with parameters of motor and exploratory behavior.

Results: V3'' differed significantly between baseline and either dose of L-DOPA/benserazide. Moreover, V3'' differed significantly between L-DOPA treatment groups. After 5 mg/kg L-DOPA/benserazide, DAT binding was inversely correlated with sitting duration (1-5 min) and sitting frequency (10-15 min). After 10 mg/kg L-DOPA/benserazide, an inverse correlation was found between DAT binding and sitting duration (1-30 min), whereas DAT binding and duration of ambulatory activity (1-30 min) as well as head and shoulder motility (10-15 min) exhibited a positive correlation.

Conclusion: Challenge with 5 and 10 mg/kg L-DOPA/benserazide led to mean reductions in DAT binding by 34 and 20%, respectively. Results indicate a biphasic response with a higher effect on DAT after the lower dose of L-DOPA. The reduction in DAT binding may be interpreted in terms of competition between [123I]FP-CIT and endogenous dopamine. Moreover, there is preliminary evidence of an association between striatal DAT and motor and exploratory parameters.

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(a) Coronal [123I]FP-CIT images of the same rat head at baseline, after pretreatment with 5 mg/kg l-DOPA/benserazide, and after treatment with 10 mg/kg benserazide. The reduction in striatal DAT binding after l-DOPA is clearly visible. All images show V3′′ values; it is understood that the calculation of V3′′ is only valid for regions of specific radioligand binding such as the rat striatum. Calculations were performed using MATLAB (version 4.2c or version 6; The MathWorks Inc., Novi, Michigan, USA). (b) Striatal equilibrium ratios (V3′′) at baseline, after 5 mg/kg l-DOPA/benserazide, and after 10 mg/kg benserazide. Rendered are means and SEM. The circles represent the individual animals. DAT, dopamine transporter; [123I]FP-CIT, [123I]N-Ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane; l-DOPA, l-3,4-dihydroxyphenylalanine.
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Figure 2: (a) Coronal [123I]FP-CIT images of the same rat head at baseline, after pretreatment with 5 mg/kg l-DOPA/benserazide, and after treatment with 10 mg/kg benserazide. The reduction in striatal DAT binding after l-DOPA is clearly visible. All images show V3′′ values; it is understood that the calculation of V3′′ is only valid for regions of specific radioligand binding such as the rat striatum. Calculations were performed using MATLAB (version 4.2c or version 6; The MathWorks Inc., Novi, Michigan, USA). (b) Striatal equilibrium ratios (V3′′) at baseline, after 5 mg/kg l-DOPA/benserazide, and after 10 mg/kg benserazide. Rendered are means and SEM. The circles represent the individual animals. DAT, dopamine transporter; [123I]FP-CIT, [123I]N-Ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane; l-DOPA, l-3,4-dihydroxyphenylalanine.

Mentions: Figures 2a and 3a show characteristic images of [123I]FP-CIT accumulations on coronal slices at baseline and after challenge with 5 mg/kg l-DOPA/benserazide, 10 mg/kg l-DOPA/benserazide, and benserazide alone. Striatal [123I]FP-CIT accumulations are markedly reduced following pretreatment with both 5 mg/kg (Fig. 2a) and 10 mg/kg l-DOPA/benserazide (Fig. 3a).


Effects of L-DOPA on striatal iodine-123-FP-CIT binding and behavioral parameters in the rat.

Nikolaus S, Beu M, Hautzel H, Silva AM, Antke C, Wirrwar A, Huston JP, Müller HW - Nucl Med Commun (2013)

(a) Coronal [123I]FP-CIT images of the same rat head at baseline, after pretreatment with 5 mg/kg l-DOPA/benserazide, and after treatment with 10 mg/kg benserazide. The reduction in striatal DAT binding after l-DOPA is clearly visible. All images show V3′′ values; it is understood that the calculation of V3′′ is only valid for regions of specific radioligand binding such as the rat striatum. Calculations were performed using MATLAB (version 4.2c or version 6; The MathWorks Inc., Novi, Michigan, USA). (b) Striatal equilibrium ratios (V3′′) at baseline, after 5 mg/kg l-DOPA/benserazide, and after 10 mg/kg benserazide. Rendered are means and SEM. The circles represent the individual animals. DAT, dopamine transporter; [123I]FP-CIT, [123I]N-Ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane; l-DOPA, l-3,4-dihydroxyphenylalanine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3815148&req=5

Figure 2: (a) Coronal [123I]FP-CIT images of the same rat head at baseline, after pretreatment with 5 mg/kg l-DOPA/benserazide, and after treatment with 10 mg/kg benserazide. The reduction in striatal DAT binding after l-DOPA is clearly visible. All images show V3′′ values; it is understood that the calculation of V3′′ is only valid for regions of specific radioligand binding such as the rat striatum. Calculations were performed using MATLAB (version 4.2c or version 6; The MathWorks Inc., Novi, Michigan, USA). (b) Striatal equilibrium ratios (V3′′) at baseline, after 5 mg/kg l-DOPA/benserazide, and after 10 mg/kg benserazide. Rendered are means and SEM. The circles represent the individual animals. DAT, dopamine transporter; [123I]FP-CIT, [123I]N-Ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane; l-DOPA, l-3,4-dihydroxyphenylalanine.
Mentions: Figures 2a and 3a show characteristic images of [123I]FP-CIT accumulations on coronal slices at baseline and after challenge with 5 mg/kg l-DOPA/benserazide, 10 mg/kg l-DOPA/benserazide, and benserazide alone. Striatal [123I]FP-CIT accumulations are markedly reduced following pretreatment with both 5 mg/kg (Fig. 2a) and 10 mg/kg l-DOPA/benserazide (Fig. 3a).

Bottom Line: Challenge with 5 and 10 mg/kg L-DOPA/benserazide led to mean reductions in DAT binding by 34 and 20%, respectively.Results indicate a biphasic response with a higher effect on DAT after the lower dose of L-DOPA.The reduction in DAT binding may be interpreted in terms of competition between [123I]FP-CIT and endogenous dopamine.

View Article: PubMed Central - PubMed

Affiliation: aClinic of Nuclear Medicine, University Hospital Düsseldorf bCenter for Behavioural Neuroscience, Heinrich-Heine University, Düsseldorf cDepartment of Nuclear Medicine, Helios Clinic Krefeld GmbH, Krefeld, Germany.

ABSTRACT

Purpose: The effect of clinical L-3,4-dihydroxyphenylalanine (L-DOPA) doses on the binding of [121I]N-Ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (121[I]FP-CIT) to the rat dopamine transporter (DAT) was investigated using small animal single-photon emission computed tomography.

Materials and methods: DAT binding was measured at baseline, after challenge with the aromatic L-amino acid decarboxylase inhibitor benserazide, and after challenge with either 5 or 10 mg/kg L-DOPA plus benserazide. For baseline and challenges, striatal equilibrium ratios (V3'') were computed as an estimation of the binding potential. Moreover, striatal V3'' values were correlated with parameters of motor and exploratory behavior.

Results: V3'' differed significantly between baseline and either dose of L-DOPA/benserazide. Moreover, V3'' differed significantly between L-DOPA treatment groups. After 5 mg/kg L-DOPA/benserazide, DAT binding was inversely correlated with sitting duration (1-5 min) and sitting frequency (10-15 min). After 10 mg/kg L-DOPA/benserazide, an inverse correlation was found between DAT binding and sitting duration (1-30 min), whereas DAT binding and duration of ambulatory activity (1-30 min) as well as head and shoulder motility (10-15 min) exhibited a positive correlation.

Conclusion: Challenge with 5 and 10 mg/kg L-DOPA/benserazide led to mean reductions in DAT binding by 34 and 20%, respectively. Results indicate a biphasic response with a higher effect on DAT after the lower dose of L-DOPA. The reduction in DAT binding may be interpreted in terms of competition between [123I]FP-CIT and endogenous dopamine. Moreover, there is preliminary evidence of an association between striatal DAT and motor and exploratory parameters.

Show MeSH