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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.


Head-shoulder motility. (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 durations of head-shoulder motility 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). Insets: T-b curves obtained by plotting median values of motility durations (A) and frequencies (B) against time. Quadratic functions (y = a + bx + cx2 with a, absolute term; bx, linear term; cx2, quadratic term) were fitted to the plots of motility durations, while linear functions (y = ax + b with a, slope and b, y-intercept) were fitted to the plots of motility frequencies. For the comparisons between groups (two-tailed F test, α = 0.0167 after Bonferroni correction) the respective p values are given.
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Figure 6: Head-shoulder motility. (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 durations of head-shoulder motility 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). Insets: T-b curves obtained by plotting median values of motility durations (A) and frequencies (B) against time. Quadratic functions (y = a + bx + cx2 with a, absolute term; bx, linear term; cx2, quadratic term) were fitted to the plots of motility durations, while linear functions (y = ax + b with a, slope and b, y-intercept) were fitted to the plots of motility frequencies. For the comparisons between groups (two-tailed F test, α = 0.0167 after Bonferroni correction) the respective p values are given.

Mentions: After treatment with 5 mg/kg L-DOPA, the duration of head-shoulder motility (Figure 6A) was significantly reduced relative to vehicle in min 6–10 (p = 0.017) and min 21–25 (p = 0.010) as well as over the whole trial (p = 0.001). Differences relative to vehicle in min 11–15 (p = 0.035), min 16–20 (p = 0.038) and min 26–30 (p = 0.045) failed to reach significance after Bonferroni correction. Head-shoulder motility was also significantly shorter after with 10 mg/kg L-DOPA relative to vehicle in min 6–10, 11–15, 16–20 and 21–25 as well as from min 1–30 (0.0001 ≤ p ≤ 0.012). The differences relative to vehicle in min 1–5 with a p of 0.018 marginally failed to reach statistical significance after Bonferroni correction. Significant between-group differences were obtained from min 6.


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)

Head-shoulder motility. (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 durations of head-shoulder motility 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). Insets: T-b curves obtained by plotting median values of motility durations (A) and frequencies (B) against time. Quadratic functions (y = a + bx + cx2 with a, absolute term; bx, linear term; cx2, quadratic term) were fitted to the plots of motility durations, while linear functions (y = ax + b with a, slope and b, y-intercept) were fitted to the plots of motility frequencies. For the comparisons between groups (two-tailed F test, α = 0.0167 after Bonferroni correction) the respective p values are given.
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Related In: Results  -  Collection

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Figure 6: Head-shoulder motility. (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 durations of head-shoulder motility 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). Insets: T-b curves obtained by plotting median values of motility durations (A) and frequencies (B) against time. Quadratic functions (y = a + bx + cx2 with a, absolute term; bx, linear term; cx2, quadratic term) were fitted to the plots of motility durations, while linear functions (y = ax + b with a, slope and b, y-intercept) were fitted to the plots of motility frequencies. For the comparisons between groups (two-tailed F test, α = 0.0167 after Bonferroni correction) the respective p values are given.
Mentions: After treatment with 5 mg/kg L-DOPA, the duration of head-shoulder motility (Figure 6A) was significantly reduced relative to vehicle in min 6–10 (p = 0.017) and min 21–25 (p = 0.010) as well as over the whole trial (p = 0.001). Differences relative to vehicle in min 11–15 (p = 0.035), min 16–20 (p = 0.038) and min 26–30 (p = 0.045) failed to reach significance after Bonferroni correction. Head-shoulder motility was also significantly shorter after with 10 mg/kg L-DOPA relative to vehicle in min 6–10, 11–15, 16–20 and 21–25 as well as from min 1–30 (0.0001 ≤ p ≤ 0.012). The differences relative to vehicle in min 1–5 with a p of 0.018 marginally failed to reach statistical significance after Bonferroni correction. Significant between-group differences were obtained from min 6.

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.