Effect of acute L-Dopa pretreatment on apomorphine-induced rotational behavior in a rat model of Parkinson's disease.
Currently, reduction of apomorphine-induced rotational behavior in the 6-hydroxydopamine (6-OHDA) lesioned rat is the most utilized drug-induced paradigm for assessing functional efficacy in a rat model of Parkinson's disease (PD). Any clinically predictive animal model of PD should include a positive response to l-dopa, the standard pharmacotherapy for PD. However, the acute interaction between L-dopa and apomorphine has never been studied to determine if L-dopa pretreatment could reduce apomorphine-induced rotational behavior in a 6-OHDA lesioned rat. The present study was designed to explore whether, indeed, pretreatment with subrotational doses of L-dopa could inhibit apomorphine-induced rotations. The data indicate that L-dopa significantly reduced apomorphine-induced rotational behavior only at one dose (5.0 mg/kg) for 12 min. Based on these and other data, it is concluded that although the apomorphine-induced rotational paradigm may continue to be utilized as one additional indicator of efficacy in the 6-OHDA rat model of PD, it is not in itself a completely valid functional assay.
Mandel
R J
RJ
Department of Neuroscience, University of Florida Brain Institute, Gainesville, Florida, 32610-0244, USA.
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002230:Carbidopa / Q000494:pharmacology; D003342:Corpus Striatum / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D012399:Rotation; D013378:Substantia Nigra / Q000502:physiology; D013565:Sympatholytics
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D013565:Sympatholytics; D007980:Levodopa; D016627:Oxidopamine; D002230:Carbidopa; D001058:Apomorphine; D004298:Dopamine