Chronic L-DOPA treatment attenuates behavioral and biochemical deficits induced by unilateral lactacystin administration into the rat substantia nigra.

Abstract

The aim of the study was to determine whether the dopamine (DA) precursor l-DOPA attenuates parkinsonian-like symptoms produced by the ubiquitin-proteasome system inhibitor lactacystin. Wistar rats were injected unilaterally with lactacystin (2.5 μg/2 μl) or 6-OHDA (8 μg/2 μl) into the substantia nigra (SN) pars compacta. Four weeks after the lesion, the animals were treated chronically with l-DOPA (25 or 50 mg/kg) for two weeks. During l-DOPA treatment, the lactacystin-treated rats were tested for catalepsy and forelimb asymmetry. Rotational behavior was evaluated after apomorphine (0.25 mg/kg) and l-DOPA in both PD models. After completion of experiments, the animals were killed and the levels of DA and its metabolites in the striatum and SN were assayed. We found that acute l-DOPA administration effectively decreased catalepsy and increased the use of the compromised forelimb in the cylinder test. However, the lactacystin group did not respond to apomorphine or acute l-DOPA administration in the rotational test. Repeated l-DOPA treatment produced contralateral rotations in both PD models, but the number of rotations was much greater in the 6-OHDA-lesioned rats. Both toxins markedly (>90%) reduced the levels of DA and its metabolites in the striatum and SN, while l-DOPA diminished these decreases, especially in the SN. By demonstrating the efficacy of l-DOPA in several behavioral tests, our study confirms the usefulness of the lactacystin lesion as a model of PD. However, marked differences in the rotational response to apomorphine and l-DOPA suggest different mechanisms of neurodegeneration evoked by lactacystin and 6-OHDA.

• Authors: Jolanta Konieczny, Anna Czarnecka, Tomasz Lenda, Kinga Kamińska, Elżbieta Lorenc-Koci
• Journal: Behavioural brain research (Behav Brain Res) Vol. 261 Pg. 79-88 (Mar 15 2014) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 24361083 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Adrenergic Agents
• Antiparkinson Agents
• Cysteine Proteinase Inhibitors
• Dopamine Agonists
• 3,4-Dihydroxyphenylacetic Acid
• lactacystin
• Serotonin
• Levodopa
• Oxidopamine
• Apomorphine
• Acetylcysteine

Topics

• 3,4-Dihydroxyphenylacetic Acid (metabolism)
• Acetylcysteine (analogs & derivatives, toxicity)
• Adrenergic Agents (toxicity)
• Animals
• Antiparkinson Agents (pharmacology)
• Apomorphine (pharmacology)
• Catalepsy (chemically induced, drug therapy)
• Cysteine Proteinase Inhibitors (toxicity)
• Dopamine Agonists (pharmacology)
• Dose-Response Relationship, Drug
• Functional Laterality (drug effects)
• Levodopa (pharmacology)
• Male
• Oxidopamine (toxicity)
• Rats
• Rats, Wistar
• Reaction Time (drug effects)
• Serotonin (metabolism)
• Substantia Nigra (drug effects, injuries)