Disturbance of sensorimotor filtering in the 6-OHDA rodent model of Parkinson's disease

LIFE SCIENCES

卷:125

Article

Issy, Ana Carolina^1,2  Padovan-Neto, Fernando E.^2,3  Lazzarini, Marcio^1,3  Bortolanza, Mariza^1,2  Del-Bel, Elaine^1,2 

[1] Univ Sao Paulo, Sch Odontol Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto, SP, Brazil

[2] Ctr Interdisciplinary Res Appl Neurosci NAPNA, Ribeirao Preto, SP, Brazil

[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, Ribeirao Preto, SP, Brazil

关键词: 6-Hydroxydopamine;    Parkinson's disease model;    Basal ganglia;    L-DOPA;    Prepulse inhibition;   

DOI  :  10.1016/j.lfs.2015.01.022

来源: Elsevier

【 摘 要 】

Aims: Parkinson's disease (PD) is a movement disorder that involves non-motor symptoms including cognitive dysfunction. L-DOPA (L-3,4-dihydroxyphenylalanine), the most effective treatment for PD, might cause the development of abnormal involuntary movements and psychotic symptoms. It has been argued that a complex interaction between drug- and intrinsic disease-related components is enrolled in PD psychotic symptoms. Prepulse inhibition (PPI) is a cross-species measure of sensorimotor gating often disrupted in disorders either with basal ganglia dysfunction or with psychotomimetic drugs. There are controversial results concerning PPI in PD patients. Nevertheless, clinical studies are difficult to interpret because of differences in disease severity, concomitant medications, and comorbidities. Our aim was to investigate the functioning of sensorimotor gating in the 6-OHDA-inducing partial or complete dopaminergic degeneration of the nigrostriatal pathway. Main methods: Since several studies suggested that PD-associated psychosis results from interaction between disease-related factors and dopamine replacement, we also analyzed in rats with complete unilateral lesion of the nigrostriatal pathway the effect of L-DOPA treatment (30 mg/kg, daily) for 1,7 or 14 days. Key findings: Complete and unilateral dopaminergic striatal depletion disrupted PPI response in rats. In mice, partial dopaminergic loss in the dorsal striatum, unilateral or bilateral, did not determine PPI changes. L-DOPA treatment determined either no PPI alteration or PPI increase in the 6-OHDA-lesioned rats. Significance: Complete striatal degeneration induced by 6-OHDA discreetly reproduced the impairment of PPI found in PD patients. Additionally, L-DOPA at a therapeutical dose, despite adverse motor effects, should not induce an impairment of sensorimotor response. (C) 2015 Elsevier Inc. All rights reserved.

【 授权许可】

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