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The effects of long-term dopaminergic treatment on locomotor behavior in rats.

Oliveira de Almeida WA, Maculano Esteves A, Leite de Almeida-Júnior C, Lee KS, Kannebley Frank M, Oliveira Mariano M, Frussa-Filho R, Tufik S, Tulio de Mello M - Sleep Sci (2014)

Bottom Line: The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days.No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist.In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, Brazil.

ABSTRACT
Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder) symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL) and drug (Pramipexole-PPX) groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions.

No MeSH data available.


Related in: MedlinePlus

(A) Assessment in the Open Field of immobility time in the control (saline) and drug (pramipexole) groups. * indicates a significant increase in the immobility time of the drug group compared to the baseline level from days 1 to 64 (ANOVA. p<0.05); @ indicates a significant increase in the immobility time of the control group relative to the baseline level from days 15 to 36 of the treatment (ANOVA, p<0.05); # indicates the same day differences between the groups between days 1 and 43 and day 57 of treatment (ANOVA, p<0.05). (B) Assessment in the Open Field of total ambulation (number of quadrants) by the control (saline) and drug (pramipexole) groups. * indicates a significant reduction in total ambulation in the drug group compared to baseline from days 1 to 57 (ANOVA, p<0.05); # indicates same day differences between the groups on days 8 and 43 of treatment (ANOVA, p<0.05). H s: hundred seconds.
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f0005: (A) Assessment in the Open Field of immobility time in the control (saline) and drug (pramipexole) groups. * indicates a significant increase in the immobility time of the drug group compared to the baseline level from days 1 to 64 (ANOVA. p<0.05); @ indicates a significant increase in the immobility time of the control group relative to the baseline level from days 15 to 36 of the treatment (ANOVA, p<0.05); # indicates the same day differences between the groups between days 1 and 43 and day 57 of treatment (ANOVA, p<0.05). (B) Assessment in the Open Field of total ambulation (number of quadrants) by the control (saline) and drug (pramipexole) groups. * indicates a significant reduction in total ambulation in the drug group compared to baseline from days 1 to 57 (ANOVA, p<0.05); # indicates same day differences between the groups on days 8 and 43 of treatment (ANOVA, p<0.05). H s: hundred seconds.

Mentions: ANOVA for the repeated measures revealed significant effects for the factors groups (F(1.15)=24.027, p<0.001) and time (F(11.165)= 14.326, p<0.001) and the interaction of groups×time (F(11.165)= 4.841, p<0.001). Fig. 1A shows that the drug group exhibited a significant increase in the immobility time compared to baseline from day 1 to 64 of the treatment. It also shows a significant increase in the immobility time for the drug group compared to baseline from days 15 to 36 of the treatment. Moreover, the drug group exhibited a significant increase relative to the control group between days 1 and 43 and on day 57 of the treatment. The control group exhibited a significant increase in immobility time relative to baseline from days 15 to 36 of the treatment.


The effects of long-term dopaminergic treatment on locomotor behavior in rats.

Oliveira de Almeida WA, Maculano Esteves A, Leite de Almeida-Júnior C, Lee KS, Kannebley Frank M, Oliveira Mariano M, Frussa-Filho R, Tufik S, Tulio de Mello M - Sleep Sci (2014)

(A) Assessment in the Open Field of immobility time in the control (saline) and drug (pramipexole) groups. * indicates a significant increase in the immobility time of the drug group compared to the baseline level from days 1 to 64 (ANOVA. p<0.05); @ indicates a significant increase in the immobility time of the control group relative to the baseline level from days 15 to 36 of the treatment (ANOVA, p<0.05); # indicates the same day differences between the groups between days 1 and 43 and day 57 of treatment (ANOVA, p<0.05). (B) Assessment in the Open Field of total ambulation (number of quadrants) by the control (saline) and drug (pramipexole) groups. * indicates a significant reduction in total ambulation in the drug group compared to baseline from days 1 to 57 (ANOVA, p<0.05); # indicates same day differences between the groups on days 8 and 43 of treatment (ANOVA, p<0.05). H s: hundred seconds.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608898&req=5

f0005: (A) Assessment in the Open Field of immobility time in the control (saline) and drug (pramipexole) groups. * indicates a significant increase in the immobility time of the drug group compared to the baseline level from days 1 to 64 (ANOVA. p<0.05); @ indicates a significant increase in the immobility time of the control group relative to the baseline level from days 15 to 36 of the treatment (ANOVA, p<0.05); # indicates the same day differences between the groups between days 1 and 43 and day 57 of treatment (ANOVA, p<0.05). (B) Assessment in the Open Field of total ambulation (number of quadrants) by the control (saline) and drug (pramipexole) groups. * indicates a significant reduction in total ambulation in the drug group compared to baseline from days 1 to 57 (ANOVA, p<0.05); # indicates same day differences between the groups on days 8 and 43 of treatment (ANOVA, p<0.05). H s: hundred seconds.
Mentions: ANOVA for the repeated measures revealed significant effects for the factors groups (F(1.15)=24.027, p<0.001) and time (F(11.165)= 14.326, p<0.001) and the interaction of groups×time (F(11.165)= 4.841, p<0.001). Fig. 1A shows that the drug group exhibited a significant increase in the immobility time compared to baseline from day 1 to 64 of the treatment. It also shows a significant increase in the immobility time for the drug group compared to baseline from days 15 to 36 of the treatment. Moreover, the drug group exhibited a significant increase relative to the control group between days 1 and 43 and on day 57 of the treatment. The control group exhibited a significant increase in immobility time relative to baseline from days 15 to 36 of the treatment.

Bottom Line: The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days.No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist.In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, Brazil.

ABSTRACT
Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder) symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL) and drug (Pramipexole-PPX) groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions.

No MeSH data available.


Related in: MedlinePlus