ABSTRACT
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 æg/side) or 6-OHDA (10 æg/side) into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67 percent) or severe (~91 percent) 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 percent of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51 percent 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.
Subject(s)
Animals , Male , Rats , Anesthetics, Combined/administration & dosage , Ketamine/administration & dosage , Neuroprotective Agents/administration & dosage , Parkinson Disease/drug therapy , Substantia Nigra/drug effects , Xylazine/administration & dosage , Anesthetics, Combined/pharmacology , Biogenic Monoamines/metabolism , Corpus Striatum/metabolism , Disease Models, Animal , Immunohistochemistry , Ketamine/pharmacology , Maze Learning/drug effects , Maze Learning/physiology , Neuroprotective Agents/pharmacology , Oxidopamine , Parkinson Disease/metabolism , Parkinson Disease/pathology , Rats, Wistar , Substantia Nigra/metabolism , Substantia Nigra/pathology , Thiopental/administration & dosage , Thiopental/pharmacology , /metabolism , Xylazine/pharmacologyABSTRACT
We studied some of the characteristics of the improving effect of the non-specific adenosine receptor antagonist, caffeine, using an animal model of learning and memory. Groups of 12 adult male Wistar rats receiving caffeine (0.3-30 mg/kg, ip, in 0.1 ml/100 g body weight) administered 30 min before training, immediately after training, or 30 min before the test session were tested in the spatial version of the Morris water maze task. Post-training administration of caffeine improved memory retention at the doses of 0.3-10 mg/kg (the rats swam up to 600 cm less to find the platform in the test session, P<=0.05) but not at the dose of 30 mg/kg. Pre-test caffeine administration also caused a small increase in memory retrieval (the escape path of the rats was up to 500 cm shorter, P<=0.05). In contrast, pre-training caffeine administration did not alter the performance of the animals either in the training or in the test session. These data provide evidence that caffeine improves memory retention but not memory acquisition, explaining some discrepancies among reports in the literature
Subject(s)
Animals , Male , Rats , Caffeine , Central Nervous System Stimulants , Maze Learning , Memory , Analysis of Variance , Caffeine , Central Nervous System Stimulants , Rats, Inbred WF , Rats, WistarABSTRACT
Os efeitos do extrato etanólico da planta tóxica Pseudocalymma elegans (Vell.) Kuhlm. sobre o comportamento de camundongos foi estudado. Camundongos que receberam injeçöes intraperitoneais (i.p.), nas doses de 1.6 a 3g/kg de peso corporal, apresentaram convulsöes e morreram com uma latência média de 8 min. A LD50 foi estimada em 1.8g/kg. Os camundongos que receberam 1g/kg (i.p.) do extrato apresentaram um maior número de "rearings" e um maior tempo de "freezing" do que o grupo controle, quando observados em um campo aberto 30 min após a injeçäo. Durante o tempo em que esses animais foram observados no campo aberto näo ocorreram alteraçöes significativas no número de cruzamentos, tempo de "grooming" e número de bolos fecais. Quando esses animais foram colocados em um labirinto em cruz elevado exploraram menos os braços abertos do labirinto que os animais controle: apresentaram uma menor porcentagem de entradas e uma menor porcentagem de tempo de permanência nos braços abertos do labirinto. Esses animais apresentaram também uma menor atividade locomotora medida de forma automatizada e nenhuma alteraçäo no tônus muscular, avaliado pelo tempo de permanência em um arame esticado. Os três primeiros testes sugerem que a administraçäo de doses moderadas do extrato desencadeia um efeito "ansiogênico" contrário ao observado com a administraçäo de ansiolíticos depressores do sistema nervoso central (SNC). Doses maiores do extrato provocam uma super-estimulaçäo do SNC com convulsöes que, eventualmente, podem contribuir para a letalidade do extrato