Behavioral and anatomical effects of long-term L-dihydroxyphenylalanine (L-DOPA) administration in rats with unilateral lesions of the nigrostriatal system.
This study investigated behavioral and anatomical changes induced by long periods of L-DOPA treatment in the unilateral rat model of Parkinson's disease. After daily injections of L-DOPA (50 mg/kg, ip) given for 1, 4, 8, or 16 weeks, behavioral sensitization, expressed by contralateral turning and changes in its pattern, increased within the first week of treatment and remained unchanged thereafter. Dyskinetic movements, affecting the trunk and limbs of all treated rats, also developed within the first week of treatment and increased further during the 16 weeks of L-DOPA treatment. L-DOPA responsiveness was also accompanied by changes at the neuronal level, as shown by changes in the expression of c-fos in the dopamine-depleted striatum. Following 1 week of L-DOPA treatment there was a marked decrease in striatal c-fos expression, compared to single injections, especially evident in the medial and ventral regions and to a lesser extent in the dorsolateral regions of the striatum. This specific regional expression of c-fos was maintained throughout the 16 weeks of L-DOPA treatment. Overall, our results show that behavioral sensitization to L-DOPA starts relatively early during the treatment and include not only an increase in contralateral turning rate but also an increase in dyskinetic movements. Persisting c-fos expression in the dorsolateral striatum might be implicated in the development of dyskinesias when L-DOPA treatment is extended for periods longer than 1 week.
Mura
Anna
A
Behavioral Neurobiology Laboratory, Swiss Federal Institute of Technology, Zurich, Schorenstrasse 16, CH-8603, Schwerzenbach, Switzerland. mura@toxi.biol.ethz.ch
Mintz
Matti
M
Feldon
Joram
J
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020820:Dyskinesias / Q000378:metabolism; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
D007980:Levodopa; D016627:Oxidopamine