Behavioral alterations in rotenone model of Parkinson's disease: attenuation by co-treatment of centrophenoxine.

Abstract

Rotenone, a potent specific inhibitor of mitochondrial complex-1, appears to reproduce the behavioral features of Parkinson's disease in rats. It destroys dopaminergic neurons selectively, causing deficiency of dopamine in striatum which leads to impaired motor functions. Oxidative stress generated as a result of mitochondrial dysfunction and metabolism of dopamine has been implicated as an important factor in the etiology of Parkinson's disease. Present study explores the potential of centrophenoxine (a well known anti-aging and antioxidant drug) against rotenone induced motor dysfunction. Sprague Dawley male rats were administered with rotenone on a daily basis by subcutaneous injection of dose: 2 mg/kg body weight over a period of 35 days. Data showed impaired motor function, significant increase in catalepsy, decrease in locomotor activity and decrease in muscle activity. Dopamine content of rotenone treated animals was found to decrease significantly and lipid peroxidation was found to increase significantly in rotenone treated animals when compared with co-treated group. Co-treatment with centrophenoxine (100 mg/kg i.p. for 35 days) significantly attenuated the extent of motor dysfunction and changes in the level of dopamine and lipid peroxidation induced by rotenone toxicity. Thus, the present study provides evidence that centrophenoxine co-treatment attenuates rotenone induced motor dysfunction by virtue of its antioxidant action.

• Authors: Bimla Nehru, Ranjeet Verma, Pooja Khanna, Suresh Kumar Sharma
• Journal: Brain research (Brain Res) Vol. 1201 Pg. 122-7 (Mar 27 2008) ISSN: 0006-8993 [Print] Netherlands
• PMID: 18308296 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Neuroprotective Agents
• Neurotoxins
• Uncoupling Agents
• Rotenone
• rotenonone
• Meclofenoxate
• Dopamine

Topics

• Animals
• Antioxidants (pharmacology)
• Behavior, Animal (drug effects, physiology)
• Brain (drug effects, metabolism)
• Catalepsy (chemically induced, drug therapy, prevention & control)
• Disease Models, Animal
• Dopamine (metabolism)
• Drug Administration Schedule
• Drug Interactions (physiology)
• Lipid Peroxidation (drug effects, physiology)
• Male
• Meclofenoxate (pharmacology)
• Motor Activity (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Neurotoxins (antagonists & inhibitors, toxicity)
• Oxidative Stress (drug effects, physiology)
• Parkinsonian Disorders (drug therapy, metabolism, physiopathology)
• Rats
• Rats, Sprague-Dawley
• Rotenone (analogs & derivatives, antagonists & inhibitors, toxicity)
• Treatment Outcome
• Uncoupling Agents (antagonists & inhibitors, toxicity)