title: Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes.
abstract: Coadministration of entacapone with levodopa attenuates motor complications in experimental models of Parkinson's disease. The mechanisms underlying entacapone effects are unknown. We investigated the effect of entacapone, on: long-duration response (LDR) to levodopa, levodopa-induced postsynaptic pharmacodynamic mechanisms and molecular changes in hemiparkinsonian rats. 6-Hydroxydopamine-unilaterally lesioned rats were treated with levodopa (25 mg/kg)+vehicle; levodopa+entacapone (30 mg/kg) or saline, twice daily for 22 days. The LDR and the apomorphine-induced rotations were measured. In situ hybridization was performed measuring the expression of striatal preproenkephalin, preprodynorphin and dopamine D-3 receptor mRNAs, subthalamic cytochrome oxidase mRNA and nigral glutamic acid decarboxylase mRNA. Entacapone potentiated the LDR but did not modify either the apomorphine-induced rotational behavior or the molecular changes. Our results suggest that the effects of entacapone on levodopa-induced motor response are not mediated by postsynaptic mechanisms and that administration of entacapone is not able to normalize the molecular alterations induced by levodopa in the basal ganglia.
authors: Laboratori de Neurologia Experimental, Area de Neurociències, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. cmarin@clinic.ub.es
authors: C
authors: C
authors: Marin
authors: E
authors: E
authors: Aguilar
authors: G
authors: G
authors: Mengod
authors: R
authors: R
authors: Cortés
authors: M C
authors: MC
authors: Rodríguez-Oroz
authors: J A
authors: JA
authors: Obeso
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002396:Catechols / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004399:Dynorphins / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D004745:Enkephalins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000503:physiopathology*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3 / Q000235:genetics; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology; D020530:Subthalamus / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D002396:Catechols; D004745:Enkephalins; D009570:Nitriles; D011498:Protein Precursors; D012333:RNA, Messenger; D050637:Receptors, Dopamine D3; C036448:pre-prodynorphin; D007980:Levodopa; C071192:entacapone; D004399:Dynorphins; C033660:preproenkephalin; D003576:Electron Transport Complex IV; D005968:Glutamate Decarboxylase; D001058:Apomorphine