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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.


Rearing. (A) duration (s) and (B) frequency (n) after vehicle (0.9% saline), 5 mg/kg L-DOPA and 10 mg/kg L-DOPA. The figure shows box and whisker plots of median rearing durations during the whole time of testing (gray shade) and in the individual 5-min time bins. 25-/75-percentiles are given in the boxes, while 25-/95-percentiles are represented by the whiskers. The circles represent the individual animals. For significant between-group differences the respective p values are given (two-tailed Mann–Whitney U test, α = 0.0167 after Bonferroni correction). Inset: T-b curves obtained by plotting median values of rearing durations (A) and rearing frequencies (B) against time and fitting exponential functions (y(t) = a * exp (−K * x) + plateau with a, value at the time t; −K, rate constant; t, time) to these data. For the comparisons between treatment groups (two-tailed F test, α = 0.0167 after Bonferroni correction) the respective p values are given.
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Figure 5: Rearing. (A) duration (s) and (B) frequency (n) after vehicle (0.9% saline), 5 mg/kg L-DOPA and 10 mg/kg L-DOPA. The figure shows box and whisker plots of median rearing durations during the whole time of testing (gray shade) and in the individual 5-min time bins. 25-/75-percentiles are given in the boxes, while 25-/95-percentiles are represented by the whiskers. The circles represent the individual animals. For significant between-group differences the respective p values are given (two-tailed Mann–Whitney U test, α = 0.0167 after Bonferroni correction). Inset: T-b curves obtained by plotting median values of rearing durations (A) and rearing frequencies (B) against time and fitting exponential functions (y(t) = a * exp (−K * x) + plateau with a, value at the time t; −K, rate constant; t, time) to these data. For the comparisons between treatment groups (two-tailed F test, α = 0.0167 after Bonferroni correction) the respective p values are given.

Mentions: After 5 mg/kg L-DOPA, rats reared (Figure 5A) for a significantly shorter time compared to vehicle-treated animals over the whole trial (p = 0.004). Differences relative to vehicle in min 11–15 (p = 0.022), min 21–25 (p = 0.020) and min 26–30 (p = 0.038) did not reach significance after Bonferroni correction. Rearing was also significantly shorter after 10 mg/kg L-DOPA compared to vehicle-treated rats in min 21–25 (p = 0.009) as well as over the whole trial (p = 0.001). Differences relative to vehicle in min 11–15 (p = 0.031) and min 16–20 (p = 0.022) and min 21–25 failed to reach significance after Bonferroni correction. Significant between-group differences emerged around min 21.


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)

Rearing. (A) duration (s) and (B) frequency (n) after vehicle (0.9% saline), 5 mg/kg L-DOPA and 10 mg/kg L-DOPA. The figure shows box and whisker plots of median rearing durations during the whole time of testing (gray shade) and in the individual 5-min time bins. 25-/75-percentiles are given in the boxes, while 25-/95-percentiles are represented by the whiskers. The circles represent the individual animals. For significant between-group differences the respective p values are given (two-tailed Mann–Whitney U test, α = 0.0167 after Bonferroni correction). Inset: T-b curves obtained by plotting median values of rearing durations (A) and rearing frequencies (B) against time and fitting exponential functions (y(t) = a * exp (−K * x) + plateau with a, value at the time t; −K, rate constant; t, time) to these data. For the comparisons between treatment groups (two-tailed F test, α = 0.0167 after Bonferroni correction) the respective p values are given.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Rearing. (A) duration (s) and (B) frequency (n) after vehicle (0.9% saline), 5 mg/kg L-DOPA and 10 mg/kg L-DOPA. The figure shows box and whisker plots of median rearing durations during the whole time of testing (gray shade) and in the individual 5-min time bins. 25-/75-percentiles are given in the boxes, while 25-/95-percentiles are represented by the whiskers. The circles represent the individual animals. For significant between-group differences the respective p values are given (two-tailed Mann–Whitney U test, α = 0.0167 after Bonferroni correction). Inset: T-b curves obtained by plotting median values of rearing durations (A) and rearing frequencies (B) against time and fitting exponential functions (y(t) = a * exp (−K * x) + plateau with a, value at the time t; −K, rate constant; t, time) to these data. For the comparisons between treatment groups (two-tailed F test, α = 0.0167 after Bonferroni correction) the respective p values are given.
Mentions: After 5 mg/kg L-DOPA, rats reared (Figure 5A) for a significantly shorter time compared to vehicle-treated animals over the whole trial (p = 0.004). Differences relative to vehicle in min 11–15 (p = 0.022), min 21–25 (p = 0.020) and min 26–30 (p = 0.038) did not reach significance after Bonferroni correction. Rearing was also significantly shorter after 10 mg/kg L-DOPA compared to vehicle-treated rats in min 21–25 (p = 0.009) as well as over the whole trial (p = 0.001). Differences relative to vehicle in min 11–15 (p = 0.031) and min 16–20 (p = 0.022) and min 21–25 failed to reach significance after Bonferroni correction. Significant between-group differences emerged around min 21.

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.