title: Nitrosative and cognitive effects of chronic L-DOPA administration in rats with intra-nigral 6-OHDA lesion.
abstract: Besides motor disturbances, other symptoms found in the early stage of Parkinson's disease (PD) are deficits in both learning and memory. The nigro-striatal-cortical pathway is affected in this pathology, with this neuronal circuit involved in cognitive processes such as spatial working memory (SWM). However, cognitive dysfunction appears even when the patients are receiving L-DOPA treatment. There is evidence that the dopamine metabolism formed by L-DOPA generates free radicals such as nitric oxide, which may cause damage through the nitrosative stress (NS). The aim of this study was to evaluate both the effects of chronic L-DOPA administration on SWM and the production of NS in rats using an intra-nigral lesion caused by 6-hydroxydopamine (6-OHDA). Post-lesion, the animals were administered orally with L-DOPA/Carbidopa (100-mg/kg) for 20 days. An SWM task in a Morris water maze was conducted post-treatment. Nitrite levels and immunoreactivity of 3-Nitrotyrosine (3-NT), Inducible Nitric Oxide Synthase (iNOS), Glial Fibrillary Acidic Protein (GFAP), and Tyrosine Hydroxylase (TH) were evaluated in the substantia nigra pars compacta, the dorsal striatum and the medial prefrontal cortex. Our results show that chronic L-DOPA administration in rats with intra-nigral 6-OHDA-lesion caused significant increases in SWM deficit, nitrite levels and the immunoreactivity of 3-NT, iNOS and GFAP in the nigro-striatal-cortical pathway. These facts suggest that as L-DOPA can induce NS in rats with dopaminergic intra-nigral lesion, it could play a key role in the impairment of the SWM, and thus can be considered as a toxic mechanism that induces cognitive deficit in PD patients.
authors: Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur y Avenida San Claudio, C.U. Edificio 105C Colonia, Jardines de San Manuel AP, 72570 Puebla, Mexico. Electronic address: gabbo_fry@hotmail.com.
authors: G
authors: G
authors: Ramírez-García
authors: Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur y Avenida San Claudio, C.U. Edificio 105C Colonia, Jardines de San Manuel AP, 72570 Puebla, Mexico. Electronic address: vpalafoxsanchez@gmail.com.
authors: V
authors: V
authors: Palafox-Sánchez
authors: Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur y Avenida San Claudio, C.U. Edificio 105C Colonia, Jardines de San Manuel AP, 72570 Puebla, Mexico. Electronic address: ilhlimon@yahoo.com.mx.
authors: I D
authors: ID
authors: Limón
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000633:toxicity*; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002230:Carbidopa / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005911:Gliosis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007980:Levodopa / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D065842:Pars Compacta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D016627:Oxidopamine; D002230:Carbidopa
keywords: Parkinson’s disease; astroglyosis; l-DOPA; nitrosative stress; spatial working memory