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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.


Sitting. (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 sitting 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). Insets: T-b curves obtained by plotting median values of sitting durations (A) and sitting frequencies (B) against time. Linear functions (y = ax + b with a, slope and b, y-intercept) were fitted to the plots of sitting durations, whereas quadrtatic functions (y = a + bx + cx2 with a, absolute term; bx, linear term; cx2, quadratic term) were fitted to the plots of sitting frequencies. 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 4: Sitting. (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 sitting 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). Insets: T-b curves obtained by plotting median values of sitting durations (A) and sitting frequencies (B) against time. Linear functions (y = ax + b with a, slope and b, y-intercept) were fitted to the plots of sitting durations, whereas quadrtatic functions (y = a + bx + cx2 with a, absolute term; bx, linear term; cx2, quadratic term) were fitted to the plots of sitting frequencies. For the comparisons between treatment groups (two-tailed F test, α = 0.0167 after Bonferroni correction) the respective p values are given.

Mentions: Animals treated with 5 mg/kg L-DOPA exhibited significantly longer sitting behavior (Figure 4A) in min 21–25 (p = 0.005) as well as throughout the whole trial (p = 0.004) compared to rats treated with vehicle. Differences between 5 mg/kg and vehicle in min 1–5 (p = 0.053) and min 16–20 (p = 0.019) failed to reach significance after Bonferroni correction. After 10 mg/kg L-DOPA, rats sat quietly for a significantly longer time than in the vehicle condition in min 6–10, 16–20 and 21–25 as well as throughout the whole trial (0.0001 ≤ p ≤ 0.012). Significant between-group differences were obvious from min 6–10 but temporarily disappeared during the third time frame (min 11–15).


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)

Sitting. (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 sitting 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). Insets: T-b curves obtained by plotting median values of sitting durations (A) and sitting frequencies (B) against time. Linear functions (y = ax + b with a, slope and b, y-intercept) were fitted to the plots of sitting durations, whereas quadrtatic functions (y = a + bx + cx2 with a, absolute term; bx, linear term; cx2, quadratic term) were fitted to the plots of sitting frequencies. 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 4: Sitting. (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 sitting 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). Insets: T-b curves obtained by plotting median values of sitting durations (A) and sitting frequencies (B) against time. Linear functions (y = ax + b with a, slope and b, y-intercept) were fitted to the plots of sitting durations, whereas quadrtatic functions (y = a + bx + cx2 with a, absolute term; bx, linear term; cx2, quadratic term) were fitted to the plots of sitting frequencies. For the comparisons between treatment groups (two-tailed F test, α = 0.0167 after Bonferroni correction) the respective p values are given.
Mentions: Animals treated with 5 mg/kg L-DOPA exhibited significantly longer sitting behavior (Figure 4A) in min 21–25 (p = 0.005) as well as throughout the whole trial (p = 0.004) compared to rats treated with vehicle. Differences between 5 mg/kg and vehicle in min 1–5 (p = 0.053) and min 16–20 (p = 0.019) failed to reach significance after Bonferroni correction. After 10 mg/kg L-DOPA, rats sat quietly for a significantly longer time than in the vehicle condition in min 6–10, 16–20 and 21–25 as well as throughout the whole trial (0.0001 ≤ p ≤ 0.012). Significant between-group differences were obvious from min 6–10 but temporarily disappeared during the third time frame (min 11–15).

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.