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Relationship between L-DOPA-induced reduction in motor and exploratory activity and degree of DAT binding in the rat.

Nikolaus S, Beu M, De Souza Silva AM, Huston JP, Hautzel H, Chao OY, Antke C, Müller HW - Front Behav Neurosci (2014)

Bottom Line: Both L-DOPA doses significantly reduced DAT binding and led to significantly less head-shoulder motility and more sitting relative to vehicle.Analysis of time-behavior (t-b) curves showed that L-DOPA-treated animals relative to vehicle exhibited (1) a faster rate of increase in duration of sitting; (2) a slower rate of increase in duration of head-shoulder motility; and (3) a slower rate of decrease in frequency of head-shoulder motility.The reductions of striatal DAT binding after L-DOPA challenges reflected elevated concentrations of synaptic DA.

View Article: PubMed Central - PubMed

Affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf Düsseldorf, Germany.

ABSTRACT

Purpose: The present study assessed the influence of L-DOPA administration on neostriatal dopamine (DA) transporter (DAT) binding in relation to motor and exploratory behaviors in the rat.

Methods: Rats received injections of 5 mg/kg L-DOPA, 10 mg/kg L-DOPA or vehicle. Motor and exploratory behaviors were assessed for 30 min in an open field prior to administration of [(123)I]FP-CIT. Dopamine transporter binding was measured with small animal single-photon emission computed tomography (SPECT) 2 h after radioligand administration for 60 min.

Results: Both L-DOPA doses significantly reduced DAT binding and led to significantly less head-shoulder motility and more sitting relative to vehicle. Moreover, 10 mg/kg L-DOPA induced less distance traveled and ambulation than 5 mg/kg L-DOPA. Analysis of time-behavior (t-b) curves showed that L-DOPA-treated animals relative to vehicle exhibited (1) a faster rate of increase in duration of sitting; (2) a slower rate of increase in duration of head-shoulder motility; and (3) a slower rate of decrease in frequency of head-shoulder motility.

Conclusions: The reductions of striatal DAT binding after L-DOPA challenges reflected elevated concentrations of synaptic DA. L-DOPA-treated animals showed less head-shoulder motility and more sitting than vehicle-treated animals, indicating an association between less behavioral activity and increased availability of striatal DA. The faster increase of sitting duration to a higher final level and the slower increase of head-shoulder motility to a lower final level relative to controls may be interpreted in terms on behavioral habituation to a novel environment.

No MeSH data available.


(A) Coronal [123I]FP-CIT images of rat heads after pre-treatment with vehicle (0.9% saline), 5 mg/kg L-DOPA and 10 mg/kg L-DOPA. The reduction in striatal DAT binding after both L-DOPA doses 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, USA). (B) Striatal equilibrium ratios (V3”) after vehicle, 5 mg/kg L-DOPA and after 10 mg/kg L-DOPA. Rendered are means and standard deviations of the means. The circles represent the individual animals. For significant between-group differences the respective p values are given (two-tailed independent t test, α = 0.0167 after Bonferroni correction).
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Figure 1: (A) Coronal [123I]FP-CIT images of rat heads after pre-treatment with vehicle (0.9% saline), 5 mg/kg L-DOPA and 10 mg/kg L-DOPA. The reduction in striatal DAT binding after both L-DOPA doses 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, USA). (B) Striatal equilibrium ratios (V3”) after vehicle, 5 mg/kg L-DOPA and after 10 mg/kg L-DOPA. Rendered are means and standard deviations of the means. The circles represent the individual animals. For significant between-group differences the respective p values are given (two-tailed independent t test, α = 0.0167 after Bonferroni correction).

Mentions: Figure 1A shows characteristic images of [123I]FP-CIT accumulations on coronal slices of rat brains after treatment with vehicle, 5 mg/kg L-DOPA or 10mg/kg L-DOPA. Striatal [123I]FP-CIT accumulations were markedly reduced following challenge with both 5 and 10 mg/kg L-DOPA.


Relationship between L-DOPA-induced reduction in motor and exploratory activity and degree of DAT binding in the rat.

Nikolaus S, Beu M, De Souza Silva AM, Huston JP, Hautzel H, Chao OY, Antke C, Müller HW - Front Behav Neurosci (2014)

(A) Coronal [123I]FP-CIT images of rat heads after pre-treatment with vehicle (0.9% saline), 5 mg/kg L-DOPA and 10 mg/kg L-DOPA. The reduction in striatal DAT binding after both L-DOPA doses 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, USA). (B) Striatal equilibrium ratios (V3”) after vehicle, 5 mg/kg L-DOPA and after 10 mg/kg L-DOPA. Rendered are means and standard deviations of the means. The circles represent the individual animals. For significant between-group differences the respective p values are given (two-tailed independent t test, α = 0.0167 after Bonferroni correction).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4269131&req=5

Figure 1: (A) Coronal [123I]FP-CIT images of rat heads after pre-treatment with vehicle (0.9% saline), 5 mg/kg L-DOPA and 10 mg/kg L-DOPA. The reduction in striatal DAT binding after both L-DOPA doses 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, USA). (B) Striatal equilibrium ratios (V3”) after vehicle, 5 mg/kg L-DOPA and after 10 mg/kg L-DOPA. Rendered are means and standard deviations of the means. The circles represent the individual animals. For significant between-group differences the respective p values are given (two-tailed independent t test, α = 0.0167 after Bonferroni correction).
Mentions: Figure 1A shows characteristic images of [123I]FP-CIT accumulations on coronal slices of rat brains after treatment with vehicle, 5 mg/kg L-DOPA or 10mg/kg L-DOPA. Striatal [123I]FP-CIT accumulations were markedly reduced following challenge with both 5 and 10 mg/kg L-DOPA.

Bottom Line: Both L-DOPA doses significantly reduced DAT binding and led to significantly less head-shoulder motility and more sitting relative to vehicle.Analysis of time-behavior (t-b) curves showed that L-DOPA-treated animals relative to vehicle exhibited (1) a faster rate of increase in duration of sitting; (2) a slower rate of increase in duration of head-shoulder motility; and (3) a slower rate of decrease in frequency of head-shoulder motility.The reductions of striatal DAT binding after L-DOPA challenges reflected elevated concentrations of synaptic DA.

View Article: PubMed Central - PubMed

Affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf Düsseldorf, Germany.

ABSTRACT

Purpose: The present study assessed the influence of L-DOPA administration on neostriatal dopamine (DA) transporter (DAT) binding in relation to motor and exploratory behaviors in the rat.

Methods: Rats received injections of 5 mg/kg L-DOPA, 10 mg/kg L-DOPA or vehicle. Motor and exploratory behaviors were assessed for 30 min in an open field prior to administration of [(123)I]FP-CIT. Dopamine transporter binding was measured with small animal single-photon emission computed tomography (SPECT) 2 h after radioligand administration for 60 min.

Results: Both L-DOPA doses significantly reduced DAT binding and led to significantly less head-shoulder motility and more sitting relative to vehicle. Moreover, 10 mg/kg L-DOPA induced less distance traveled and ambulation than 5 mg/kg L-DOPA. Analysis of time-behavior (t-b) curves showed that L-DOPA-treated animals relative to vehicle exhibited (1) a faster rate of increase in duration of sitting; (2) a slower rate of increase in duration of head-shoulder motility; and (3) a slower rate of decrease in frequency of head-shoulder motility.

Conclusions: The reductions of striatal DAT binding after L-DOPA challenges reflected elevated concentrations of synaptic DA. L-DOPA-treated animals showed less head-shoulder motility and more sitting than vehicle-treated animals, indicating an association between less behavioral activity and increased availability of striatal DA. The faster increase of sitting duration to a higher final level and the slower increase of head-shoulder motility to a lower final level relative to controls may be interpreted in terms on behavioral habituation to a novel environment.

No MeSH data available.