Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease

There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mix...

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Main Authors: M.M. Ferro, M.E.M. Angelucci, J.A. Anselmo-Franci, N.S. Canteras, C. Da Cunha
Format: Article
Language:English
Published: Associação Brasileira de Divulgação Científica 2007-01-01
Series:Brazilian Journal of Medical and Biological Research
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000100012
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spelling doaj-035c5e2d79ea4b86afc9971414a76a9e2020-11-24T23:18:50ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2007-01-014018996Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's diseaseM.M. FerroM.E.M. AngelucciJ.A. Anselmo-FranciN.S. CanterasC. Da CunhaThere is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg) and xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease. The bilateral infusion of MPTP (100 µg/side) or 6-OHDA (10 µg/side) into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67%) or severe (~91%) loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33% of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000100012Neuroprotection6-Hydroxydopamine1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridineKetamineParkinson's disease
collection DOAJ
language English
format Article
sources DOAJ
author M.M. Ferro
M.E.M. Angelucci
J.A. Anselmo-Franci
N.S. Canteras
C. Da Cunha
spellingShingle M.M. Ferro
M.E.M. Angelucci
J.A. Anselmo-Franci
N.S. Canteras
C. Da Cunha
Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease
Brazilian Journal of Medical and Biological Research
Neuroprotection
6-Hydroxydopamine
1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridine
Ketamine
Parkinson's disease
author_facet M.M. Ferro
M.E.M. Angelucci
J.A. Anselmo-Franci
N.S. Canteras
C. Da Cunha
author_sort M.M. Ferro
title Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease
title_short Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease
title_full Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease
title_fullStr Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease
title_full_unstemmed Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease
title_sort neuroprotective effect of ketamine/xylazine on two rat models of parkinson's disease
publisher Associação Brasileira de Divulgação Científica
series Brazilian Journal of Medical and Biological Research
issn 0100-879X
1414-431X
publishDate 2007-01-01
description There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg) and xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease. The bilateral infusion of MPTP (100 µg/side) or 6-OHDA (10 µg/side) into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67%) or severe (~91%) loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33% of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.
topic Neuroprotection
6-Hydroxydopamine
1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridine
Ketamine
Parkinson's disease
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000100012
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