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Effects of oligonucleotide antisense to dopamine D(1A) receptor messenger RNA in a rodent model of LID (levodopa-induced dyskinesia). Dyskinesias are abnormal involuntary movements which develop as a side-effect of long-term treatment with levodopa in patients with Parkinson's disease. The pathophysiology underlying these dyskinesias remains unclear, although, it has been suggested that heightened activity of dopamine D(1) receptor-bearing striatonigral neurons may play a key role. Chronic pulsatile levodopa administration to hemiparkinsonian rats results in sensitization of rotational responses to apomorphine. This sensitization is thought to be analogous to LID in humans. In these studies, we further clarify the role of the dopamine D(1A) receptor in this rodent model of LID using an in vivo oligonucleotide antisense approach. Hemiparkinsonian rats received twice daily injections of levodopa for three weeks followed by intrastriatal infusion of dopamine D(1A) receptor antisense (7nmol/day, three days), a scrambled missense control sequence, or saline. Those animals treated with antisense displayed significantly fewer apomorphine-induced rotations than saline- or missense-treated controls. By reducing dopamine D(1A) receptor expression, we were able to attenuate sensitization of the response to apomorphine resulting from chronic pulsatile levodopa treatment. Thus, the dopamine D(1A) receptor appears to play a significant role in LID and warrants further examination. These findings may have important implications for the development of selective treatment strategies designed to alleviate parkinsonian symptoms, while minimizing motor complications. Neuroscience 2000 Jun 1;98(1):61-67 Van Kampen JM, Stoessl AJ Faculty of Medicine, University of British Columbia, B.C., V6T 2B5, Vancouver, Canada PMID: 10858612 janet paterson 53 now / 44 dx cd / 43 onset cd / 41 dx pd / 37 onset pd tel: 613 256 8340 url: "http://www.geocities.com/janet313/" email: [log in to unmask] smail: POBox 171 Almonte Ontario K0A 1A0 Canada