The neurobehavioral changes induced by bilateral rotenone lesion in medial forebrain bundle of rats are reversed by L-DOPA.
Rotenone (an inhibitor of mitochondrial complex I) has been proposed as a model of Parkinson's disease (PD) as it induces nigrostriatal degeneration associated with alpha-synuclein inclusions. So far, only peripherally administered rotenone has been used as a model of PD. There has not been any investigation on the neurobehavioral changes induced by bilateral lesions of dopaminergic neurons by rotenone in rats. In the present study, rotenone (3 microg) was administered bilaterally stereotaxically into the medial forebrain bundle (MFB) to produce parkinsonian symptoms. Behavioural and biochemical data showed a strong increase in catalepsy, a decrease in locomotor activity and a significant depletion of dopamine levels in the striatum as compared to sham-lesioned animals. If the locomotor deficits are caused by the depletion of dopaminergic neurons, then L-DOPA should counteract motor deficits because L-DOPA therapy reverses mostly all motor deficits in human Parkinsonian patients. To examine the effectiveness of L-DOPA in reversing the motor deficit in rats, two different doses of L-DOPA (5 and 10 mg/kg) in combination with the peripheral amino acid decarboxylase inhibitor benserazide were daily administrated intraperitonially for a period of 31 days lesioned animals. L-DOPA plus benserazide counteracted catalepsy dose-dependently and increased locomotor activity. The results indicate that rotenone infused into the MFB destroys dopaminergic neurons, induces pakinsonian symptoms that are reversed by the clinically effective anti-parkinsonian drug L-DOPA. Therefore, sterotaxically infused rotenone may be useful for screening drugs for the treatment of PD.
Alam
M
M
Zoological Institute, Neuropharmacology, University of Tuebingen, Morgenstelle 28E, Tuebingen 72076, Germany.
Mayerhofer
A
A
Schmidt
W J
WJ
D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000032:analysis; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012402:Rotenone; D018709:Statistics, Nonparametric; D013997:Time Factors
D000978:Antiparkinson Agents; D012402:Rotenone; D007980:Levodopa; D004298:Dopamine