Naloxone reverses L-dopa induced overstimulation effects in a Parkinson's disease animal model analogue.
Chronic L-DOPA treatment of Parkinson's disease frequently leads to the development of motoric overstimulation and hyperkinetic movements. To investigate this problem in the laboratory, rats surgically altered by unilateral 6-hydroxydopamine lesions (6-OHDA) were chronically treated with one L-DOPA (10 mg/kg i.p.) injection per day for 20 days. In this 6-OHDA rotation model, the unilateral dopamine denervation results in a profound contralateral sensory-motor neglect and the animals spontaneously rotate in a direction ipsilateral to the dopamine depleted hemisphere. Initially, the L-DOPA treatment did not alter the response bias but after several weeks, the response bias was reversed and the animals rotated in the formerly akinetic direction, contralaterally, at a significantly higher level. Using this overstimulation effect as an analogue of the clinically observed L-DOPA overstimulation, animals were given naloxone in conjunction with the L-DOPA treatment. Naloxone (0.10, 0.25 and 0.50 mg/kg i.p.) produced a dose related decrease in the L-DOPA induced contralateral rotation. Consistent with an expected selective effect on the L-DOPA induced rotation, a dose related increase in ipsilateral rotation was observed. These results suggest that naloxone can attenuate the overstimulation effect of L-DOPA and that this effect is not attributable to non-specific response suppression effects.
Carey
R J
RJ
Research and Development Service, VA Medical Center, Syracuse, NY.
D000818:Animals; D002230:Carbidopa / Q000008:administration & dosage / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D006892:Hydroxydopamines / Q000008:administration & dosage / Q000494:pharmacology; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D006892:Hydroxydopamines; D009270:Naloxone; D007980:Levodopa; D016627:Oxidopamine; D002230:Carbidopa; D004298:Dopamine