L-dopa-induced desensitization depends on 5-hydroxytryptamine imbalance in hemiparkinsonian rats.
We have shown before that 2-week intrastriatal L-3,4-dihydroxyphenylalanine (L-dopa) infusion significantly decreased contralateral rotations induced by acute intraperitoneal L-dopa/carbidopa and increased striatal tryptophan hydroxylase in 6-hydroxydopamine-lesioned rats. Here, we examined the effect of acutely administered L-dopa (10 microg) into 6-hydroxydopamine-lesioned rat striata under the inhibition of tryptophan hydroxylase by 4-chloro-DL-phenylalanine. Acute intrastriatal L-dopa infusion significantly decreased contralateral rotations induced by intraperitoneal L-dopa/carbidopa (10/30 mg/kg) 1 and 7 days after intrastriatal L-dopa. This desensitization to L-dopa occurred only when there was a striatal 5-hydroxytryptamine (5-HT) imbalance, not when 5-HT levels in the intact and lesioned sides were similar, either very low (day 1 postinfusion) or similarly recovered (day 7 postinfusion). We conclude that 5-HT plays a significant role in the striatal dopaminergic imbalance that evokes the rotational behavior.
Kääriäinen
Tiina M
TM
Department of Pharmacology and Toxicology, University of Kuopio, Finland. Tiina.Kaariainen@uku.fi
García-Horsman
Juan Arturo
JA
Piltonen
Marjo
M
Männistö
Pekka T
PT
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015259:Dopamine Agents / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000503:physiopathology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009069:Movement Disorders / Q000188:drug therapy / Q000503:physiopathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D012701:Serotonin / Q000378:metabolism*; D013565:Sympatholytics; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism
D015259:Dopamine Agents; D013565:Sympatholytics; D012701:Serotonin; D007980:Levodopa; D016627:Oxidopamine; D014365:Tryptophan Hydroxylase