Oral creatine supplementation attenuates L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rats

• Published in: Behavioural brain research 2009-01, Vol.197 (1), p.90-96
• Main Authors: Valastro, Barbara, Dekundy, Andrzej, Danysz, Wojciech, Quack, Guenter
• Format: Article
• Language: English
• Subjects: Abnormal involuntary movements; Administration, Oral; Adult and adolescent clinical studies; Analysis of Variance; Animals; Basal ganglia; Behavioral psychophysiology; Biological and medical sciences; Creatine - administration & dosage; Creatine - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dietary Supplements; Disease Models, Animal; Dyskinesia, Drug-Induced - complications; Dyskinesia, Drug-Induced - metabolism; Dyskinesia, Drug-Induced - prevention & control; Energy deficit; Energy Metabolism - physiology; Enkephalins - genetics; Enkephalins - metabolism; Female; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Levodopa; Levodopa - adverse effects; Levodopa - therapeutic use; Medical sciences; Neostriatum - drug effects; Neostriatum - metabolism; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - metabolism; Organic mental disorders. Neuropsychology; Oxidopamine; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - complications; Parkinsonian Disorders - drug therapy; Parkinson’s disease; Phosphocreatine - metabolism; Protein Precursors - genetics; Protein Precursors - metabolism; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis; Statistics, Nonparametric; Striatum
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2008.08.004

L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson patients after a prolonged treatment with levodopa (L-DOPA). Since previous transcriptome and proteomic studies performed in the rat model of LID suggested important changes in striatal energy-related components, we hypothesize that oral creatine supplementation could prevent or attenuate the occurrence of LID. In this study, 6-hydroxydopamine-lesioned rats received a 2% creatine-supplemented diet for 1 month prior to L-DOPA therapy. During the 21 days of L-DOPA treatment, significant reductions in abnormal involuntary movements (AIMs) have been observed in the creatine-supplemented group, without any worsening of parkinsonism. In situ hybridization histochemistry and immunohistochemistry analysis of the striatum also showed a reduction in the levels of prodynorphin mRNA and FosB/ΔFosB-immunopositive cells in creatine-supplemented diet group, an effect that was dependant on the development of AIMs. Further investigation of the bioenergetics’ status of the denervated striatum revealed significant changes in the levels of creatine both after L-DOPA alone and with the supplemented diet. In conclusion, we demonstrated that combining L-DOPA therapy with a diet enriched in creatine could attenuate LID, which may represent a new way to control the motor complications associated with L-DOPA therapy.