Diazepam - Its effects on the development of pentylenetetrazol kindling, related learning impairments, and neuronal cell loss

Epileptics frequently experience cognitive disturbances. It was speculated that seizure activity causes neuronal cell loss which might, in part, contribute to these disturbances. To shed light on this problem, the kindling (pentylenetetrazol) model of epilepsy was used. Diazepam (DZP) was intraperitoneally injected (0.5 of 2.5 mg kg(-1)) in the course of kindling development. Six weeks after kindling completion the animals were tested for their performance in a shuttle-box and finally, the brains were processed for histological examination. It was found that DZP suppressed the expression of motor seizures. Kindled animals showed a significantly diminished shuttle-box performance. This impairment was not ameliorated by DZP. Moreover, the learning performance in control animals pretreated with DZP was low suggesting long-lasting alterations due to DZP application. In kindled animals the number of neurones in the hippocampal CA1 region was significantly reduced and this effect was counteracted by the substance. The presented data suggest that seizure suppression and a reduction in neuronal cell loss must not automatically result in improved learning performance. (C) 1997 The Italian Pharmacological Society.