Pre-treatment with dopamine agonists influence L-dopa mediated rotations without affecting abnormal involuntary movements in the 6-OHDA lesioned rat.
L-dopa induced dyskinesia is a complication of long-term L-dopa administration in patients with Parkinson's disease. This study uses the rodent model of dyskinesia to determine whether prior dopamine agonist treatment causes long-term changes that influence the development of L-dopa mediated behaviours. Rats with unilateral 6-OHDA lesions were injected with dopamine agonists (ropinirole, piribedil bromocriptine, all 1mg/kg) or saline (0.9%) daily for 21 days. Following a 1-week drug free interval L-dopa was administered for 15 days (10mg/kg with benserazide 15 mg/kg in saline s.c.). Rotational behaviour and abnormal involuntary movements (AIMs) were recorded at regular intervals. All dopamine agonists induced a contralateral rotational response on day 1, which increased in response to repeated administration but did not by themselves induce overt dyskinesias. On day 1 of L-dopa administration animals pre-treated with piribedil and ropinirole produced a more severe rotational response. In the saline pre-treated group, AIMs developed with repeated L-dopa administration, which was reflected in the increased expression of PPE-B mRNA. There was a trend for the same pattern in the dopamine agonist treated groups but this was non-significant. Therefore, while locomotor sensitivity is altered by the pre-treatment with dopamine agonists, there appears to be no increased risk of developing AIMs.
Lane
Emma L
EL
Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK. Laneel@cf.ac.uk
Dunnett
Stephen B
SB
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology*; D001971:Bromocriptine / Q000008:administration & dosage / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000150:complications / Q000188:drug therapy*; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007980:Levodopa / Q000009:adverse effects / Q000494:pharmacology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D010891:Piribedil / Q000008:administration & dosage / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013997:Time Factors
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D004745:Enkephalins; D007211:Indoles; D011498:Protein Precursors; D012333:RNA, Messenger; C046649:ropinirole; D001971:Bromocriptine; D007980:Levodopa; D016627:Oxidopamine; C033660:preproenkephalin; D010891:Piribedil