A neuropharmacological analysis of PTZ-induced kindling in mice.

Depto. de Farmacologia, Universidade Federal do Rio Grande do Sul, RS, Brazil.
General Pharmacology 08/1998; 31(1):47-50. DOI: 10.1016/S0306-3623(97)00423-0
Source: PubMed

ABSTRACT 1. Glutamate seems to play a central role in epilepsy, and kindling is considered the most useful experimental model in revealing plastic changes associated with epileptic features. 2. The aim of this study was to optimize pentylenetetrazol (PTZ)-kindling conditions in mice and analyze glutamatergic changes associated with this phenomena. 3. A significant increase (85.7%) in seizuring animals was observed after four PTZ administrations, with all subjects presenting full seizures after five administrations. 4. PTZ kindling, but not acute seizure, significantly increased (169.8%) the specific binding of [3H]glutamate in the cerebral cortex. 5. The development of PTZ-induced kindling in mice was prevented by the coadministration of phenobarbital or diazepam. 6. This study indicates that mice can be used in a reliable model of PTZ-induced kindling and that, as in rats, the kindling increases the specific [3H]glutamate binding in the cerebral cortex, therefore allowing for screening new drugs that can interfere in the plastic changes believed to underlie epileptic phenomena.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The effect of estriol, the third estrogen, was evaluated for its effect on pentylenetetrazole (PTZ)-kindling model of epileptogenesis in mice followed by evaluation on kindling-induced changes in cognitive and motor functions. Kindling was induced by once every 2 days treatment with PTZ (25 mg/kg, i.p.) for 5 weeks. The seizure severity during induction of kindling and percentage incidence of animals kindled at the end of 5 weeks was recorded. Motor function was assessed using a grip strength meter while spatial memory was assessed in a cross maze. Estriol (0.005 and 0.01 mg/kg i.p.) reduced the time for induction of kindling from 5 weeks to 3 and 2 weeks for male and female mice respectively and enhanced the percentage incidence of seizures. Clomiphene (0.9 mg/kg i.p.) delayed the development of kindling and produced anticonvulsant effects. It also partially reversed the proconvulsant effects of estriol. On grip strength test and spontaneous alternation behaviour, a significant decline was observed in kindled mice which was further reduced by pre-treatment with estriol. Both clomiphene and diazepam were unable to reverse the reduced GS of PTZ-kindled mice but enhanced the percentage alternation of such animals. The study shows that estriol has powerful proconvulsant effects. Its administration in hormone replacement therapy or other indications, thus, requires careful monitoring in patients susceptible to epileptic seizures. The anticonvulsant effects of clomiphene requires further investigations.
    Neurological Sciences 04/2014; · 1.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epilepsy is one of the most common chronic disorders affecting individuals of all ages. A greater understanding of pathogenesis in epilepsy will likely provide the basis fundamental for development of new antiepileptic therapies that aim to prevent the epileptogenesis process or modify the progression of epilepsy in addition to treatment of epilepsy symptomatically. Therefore, several investigations have embarked on advancing knowledge of the mechanism underlying epileptogenesis, understanding in mechanism of pharmacoresistance and discovering antiepileptogenic or disease-modifying therapy. Animal models play a crucial and significant role in providing additional insight into mechanism of epileptogenesis. With the help of these models, epileptogenesis process has been demonstrated to be involved in various molecular and biological pathways or processes. Hence, this article will discuss the known and postulated mechanisms of epileptogenesis and challenges in using the animal models.
    Iranian Journal of Basic Medical Science 11/2013; 16(11):1119-1132. · 0.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Arthropod venoms are potential sources of neuroactive substances, providing new tools for the design of drugs. The aim of this study was to evaluate the effects of Dinoponera quadriceps venom (DqV) on seizure models in mice induced by pentylenetetrazole (PTZ), pilocarpine, and strychnine. In the PTZ model, intraperitoneal treatment with DqV (0.5 mg/kg) increased the time until the first seizure and the percentage of survival (155.4±27.7 seconds / 12.5%, p<0.05) compared to the control group (79.75±3.97 seconds / 0%), whereas endovenous treatment (0.1 and 0.5 mg/kg) decreased the time until the first seizure (0.1 mg/kg: 77.83±5.3 seconds versus 101.0±3.3 seconds in the control group; 0.5 mg/kg: 74.43±3.9 seconds versus 101.0±3.3 seconds for the control group, p<0.05). We did not observe significant changes in the pilocarpine- and strychnine-induced seizure models. In assays that measured oxidative parameters in the PTZ model, intraperitoneal treatment with DqV (0.5 and 2.0 mg/kg) only decreased the levels of MDA and nitrite in the cortex. However, endovenous treatment with DqV (0.1 and 0.5 mg/kg) increased the levels of MDA in the cortex and hippocampus and at a dose of 0.5 mg/kg in the striatum. Moreover, increased in nitrite content was observed in all three of the brain regions analyzed. Taken together, the Dinoponera quadriceps venom caused both neuroprotective and neurotoxic effects in a PTZ-induced seizure model, and this effect was dependent on the route of administration used.
    Neurochemistry International 06/2013; · 2.66 Impact Factor