Lesion of the tuberomammillary nucleus E2-region attenuates postictal seizure protection in rats

Postictal seizure protection (PSP) is an endogenous anticonvutsant phenomenon that follows an epileptic seizure and inhibits the induction of further seizures. The tubero-mammillary nucleus (TM), located in the posterior hypothalamus, consists of five subregions and is the sole source of histaminergic neurons in the brain. To determine whether the TM is involved in PSP in rats, we tested the effects of bilateral electrolytic lesions of the TM E2-region on seizures induced by intermittent maximal. etectroshock (MES). The TM E2-region lesions significantly attenuated PSP during the intermittent MES procedure. Furthermore, intracerebroventricutar injection of alpha-fluoromethythistidine (100 mu g), a selective and irreversible histidine decarboxytase inhibitor, mimicked the attenuation of PSP induced by the lesion of TM E2-region. In addition, neurochemical experiments revealed that the TM E2-region lesions markedly decreased basal histamine levels in the cortex, hippocampus, brainstem and hypothalamus, but had no significant effect on basal glutamate and GABA levels. Moreover, intermittent MES induced a persistent decrease of brain histamine levels in both sham-operated and lesioned rats. These results indicate that through its intrinsic histaminergic system, the TM may exert powerful inhibitory function during the intermittent MES procedure and actively participate in the mechanisms of PSP. (c) 2006 Elsevier B.V. All rights reserved.