Vitamin E attenuates reserpine-induced oral dyskinesia and striatal oxidized glutathione/reduced glutathione ratio (GSSG/GSH) enhancement in rats.

The effects of a previous and concomitant treatment with vitamin E (VE) were studied on an animal model of tardive dyskinesia, i.e., the frequency of spontaneous tongue protrusions in rats treated with reserpine (RE). VE (5, 10, 20 or 40 mg/kg administered intraperitoneally, daily, for 19 days) attenuated the increase in tongue protrusion frequency induced by RE (1 mg/kg administered subcutaneously, on Days 16 and 18, 1 h after VE), which was quantified on Day 19. In a second experiment, a similar treatment with 20 mg/kg VE attenuated RE-induced increase in the striatal ratio of oxidized/reduced glutathione (GSSG/GSH), an index of the oxidative stress process. These results support the free radical hypothesis of tardive dyskinesia.

Caracterizaçäo experimental e possível participaçäo de espécies reativas de oxigênio em um modelo animal de discinesia orofacial / Experimental characterization and participation possible the species reativ of oxygen in animal model of orofacial dyskinesia

Funcionalmente incapacitaste e esteticamente d esfigurante, a discinesia tardia é considerada não apenas o principal efeito colateral decorrente do tratamento com antipsicóticos, como a principal desordem iatrogênica do movimento. Caracterizada por hipercinesias buco-linguo-mastigatórias involuntárias e por vezes irreversíveis, a discinesia tardia e desprovida de tratamentos comprovadamente eficazes a longo prazo. Paralelamente, a característica tardia de seu desenvolvimento limita acentuadamente a viabilidade de estudos clínicos prolongados adequadamente controlados. Nesse contexto, a caracterização e validação de modelos animais dessa desordem de movimento torna-se imperiosa. Em meados da década de 1990, Neisewander e colaboradores propuseram um novo modelo animal para a discinesia tardia: o aumento do número de protrusões de língua induzido pela administração repetida do depletor monoaminérgico reserpina em ratos. Esse trabalho clássico aliado a outros estudos que se seguiram, trouxeram importantes evidências em suporte a essa proposição. Com efeito, o aumento de protrusões de língua induzido pela administração repetida de reserpina em ratos preenche alguns quesitos concernentes tanto a aspectos fenomenológicos e clínicos como a hipóteses fisiopatológicas da discinesia tardia em humanos. Não obstante, enquanto a caracterização fenomenológica/temporal e farmacológica/mecanicística do modelo ainda é incipiente, sua confrontação com os preconizados fatores de risco da doença é...(au)

Concomitant development of oral dyskinesia and memory deficits in reserpine-treated male and female mice.

It has been suggested that reserpine-induced oral dyskinesia in rats may provide a new animal model of tardive dyskinesia. Both cognitive deficits and gender have been associated with the development of tardive dyskinesia. The aim of the present study was to investigate the effects of reserpine administration on the development of orofacial dyskinesia and on plus-maze discriminative avoidance task (DAT-an animal model of associative learning) in male and female mice. Male and female mice received 1.0 mg/kg reserpine or saline subcutaneously on day 1. On days 3, 6 and 8, the frequency of vacuous chewing movements (VCM) was quantified. On day 6, the DAT conditioning was performed, in a modified elevated plus-maze. In one of the enclosed arms, the animals received aversive stimulation (light and noise). On day 8, a test session was performed and the time spent by the animals in each of the enclosed arms was recorded. Our results showed that reserpine-treated male and female mice presented significantly higher VCM when compared with respective control groups in all observation days. On day 6, reserpine-treated female mice presented significantly higher VCM when compared with male mice injected with this drug. The DAT test performed on day 8 showed that the time spent in the aversive arm by saline-treated mice was significantly lower than the time spent in the non-aversive arm. This difference was not observed for reserpine-treated mice. Our results demonstrate the development of reserpine-induced oral dyskinesia in both male and female mice. While this oral dyskinesia is accompanied by a cognitive deficit in both genders, female mice tended to have more severe oral dyskinesia. It is suggested that reserpine-induced oral dyskinesia may provide a quick, simple and efficient mouse model of tardive dyskinesia.

The mitochondrial toxin 3-nitropropionic acid aggravates reserpine-induced oral dyskinesia in rats.

The effects of a previous long-term administration of the mitochondrial toxin 3-nitropropionic acid were studied on an animal model of tardive dyskinesia, i.e., the frequency of spontaneous tongue protrusions in rats repeatedly treated with reserpine. 3-Nitropropionic acid (10 or 15 mg/kg i.p., every other day for 17 days) potentiated the increase in tongue-protrusion frequency induced by reserpine (1 mg/kg, s.c., every other day for 3 days) but did not modify reserpine-induced increase in immobility duration and decrease in locomotion frequency. These results support the notion that neurotoxic events are associated with the development of tardive dyskinesia.