Does contraversive circling in the 6-OHDA-lesioned rat indicate an ability to induce motor complications as well as therapeutic effects in Parkinson's disease?
Circling behaviour in unilateral 6-OHDA-lesioned rats is interpreted as being opposite in direction to the side of the brain with highest striatal dopaminergic activation. Ipsiversive rotation indicates an action on the intact striatum, while contraversive rotation demonstrates an effect on dopamine receptors in the denervated striatum and is taken as predictive of symptomatic benefit in Parkinson's disease. But does an equivalent behavioural outcome result from stimulating the intact and denervated striatum to the same degree? We report on the behavioural responses produced by administration of L-dopa and the monoamine uptake inhibitor BTS 74,398. These were given alone, or in combination, at doses equivalent to their ED(25), ED(50) and ED(75) for inducing circling in unilateral 6-OHDA-lesioned rats. L-dopa administered alone induced dose-dependent contraversive circling while BTS 74,398 produced ipsiversive rotation. However, L-dopa and BTS 74,398 in combination, produced the same contraversive circling response as when L-dopa was administered alone. Little or no ipsiversive rotation occurred, irrespective of the combination of doses employed. This surprising finding suggests that there are major differences in the outcome of stimulating the intact and denervated striatum with the latter dominating the behavioural response. Since repeated administration of L-dopa but not BTS 74,398, sensitises rotational responses and induces abnormal movements, it may be that contraversive rotation is predictive of both clinical response in PD and the ability to induce motor complications.
Lane
E L
EL
Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London, UK. emma.lane@mphy.lu.se
Cheetham
S C
SC
Jenner
P
P
D018663:Adrenergic Agents / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal; D002722:Chlorobenzenes / Q000494:pharmacology; D003503:Cyclobutanes / Q000494:pharmacology; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000627:therapeutic use; D004347:Drug Interactions; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine / Q000627:therapeutic use / Q000633:toxicity*; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D045442:Rotarod Performance Test / Q000379:methods; D012399:Rotation; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
D018663:Adrenergic Agents; C488846:BTS 74 398; D002722:Chlorobenzenes; D003503:Cyclobutanes; D015259:Dopamine Agents; D007980:Levodopa; D016627:Oxidopamine