Effect of subthalamic nucleus or entopeduncular nucleus lesion on levodopa-induced neurochemical changes within the basal ganglia and on levodopa-induced motor alterations in 6-hydroxydopamine-lesioned rats.
Inactivation of the subthalamic nucleus (STN) or the internal segment of the pallidum (GPi)/entopeduncular nucleus (EP) by deep brain stimulation or lesioning alleviates clinical manifestations of Parkinson's disease (PD) as well as reducing the side-effects of levodopa treatment. However, the effects of STN or entopeduncular nucleus (EP) lesion on levodopa-related motor fluctuations and on neurochemical changes induced by levodopa remain largely unknown. The effects of such lesions on levodopa-induced motor alterations were studied in 6-hydroxydopamine (6-OHDA)-lesioned rats and were assessed neurochemically by analyzing the functional activity of the basal ganglia nuclei, using the expression levels of the mRNAs coding for glutamic acid decarboxylase and cytochrome oxidase as molecular markers of neuronal activity. At the striatal level, preproenkephalin (PPE) mRNA levels were analyzed. We found in 6-OHDA-lesioned rats that a unilateral STN or EP lesion ipsilateral to the 6-OHDA lesion had no effect on either the shortening in the duration of the levodopa-induced rotational response or the levodopa-induced biochemical changes in the basal ganglia nuclei. In contrast, overexpression of PPE mRNA due to levodopa treatment was reversed by the STN or EP lesion. Our study thus shows that lesion of the EP or STN may counteract some of the neurochemical changes induced by levodopa treatment within the striatum.
Périer
Céline
C
INSERM U289, Experimental Neurology and Therapeutics, Hôpital de la Salpêtrière, Paris, France.
Marin
Concepció
C
Jimenez
Anna
A
Bonastre
Mercè
M
Tolosa
Eduardo
E
Hirsch
Etienne C
EC
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000235:genetics; D004745:Enkephalins / Q000235:genetics; D020392:Entopeduncular Nucleus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000235:genetics; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
D004745:Enkephalins; D007527:Isoenzymes; D011498:Protein Precursors; D012333:RNA, Messenger; D007980:Levodopa; D016627:Oxidopamine; C033660:preproenkephalin; D003576:Electron Transport Complex IV; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1