L-DOPA reverses the hypokinetic behaviour and rigidity in rotenone-treated rats.
Peripherally and locally administered 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. If rotenone-induced symptoms represent a model of PD, than they should be counteracted by L-DOPA. To answer this question, rats were treated with rotenone 2.5 mg/kg over 48 days. Behavioural data showed a strong increase in catalepsy, a decrease in locomotor activity and biochemical data showed a significant depletion of dopamine levels in the striatum (Cpu) and substantia nigra in rotenone treated animals compared to vehicle. To examine the effectiveness of L-DOPA in reversing the motor deficit in rats, a dose of L-DOPA (10 mg/kg) in combination with the peripheral amino acid decarboxylase inhibitor benserazide were daily administrated intraperitonially for a period of 10 days in the rotenone-treated rats. This treatment counteracted catalepsy and increased locomotor activity and number of rearings but decreased inactive sitting. In this animal model (rotenone model), catalepsy tests and motor activities showed that the clinically used anti-parkinsonian drug L-DOPA substitutes rotenone-induced dopamine (DA) deficiency.
Alam
M
M
Zoological Institute, Neuropharmacology, Morgenstelle 28E, University of Tuebingen, 72076 Tuebingen, Germany.
Schmidt
W J
WJ
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000502:physiology; D001545:Benserazide / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors* / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D009127:Muscle Rigidity / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000633:toxicity*; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology; D014475:Uncoupling Agents / Q000633:toxicity*
D000978:Antiparkinson Agents; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D014475:Uncoupling Agents; D012402:Rotenone; D007980:Levodopa; D001545:Benserazide; D001142:Aromatic-L-Amino-Acid Decarboxylases; D042967:Electron Transport Complex I; D004298:Dopamine