Lesion of the tuberomammillary nucleus E2-region attenuates postictal seizure protection in rats.
Postictal seizure protection (PSP) is an endogenous anticonvulsant phenomenon that follows an epileptic seizure and inhibits the induction of further seizures. The tuberomammillary 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 electroshock (MES). The TM E2-region lesions significantly attenuated PSP during the intermittent MES procedure. Furthermore, intracerebroventricular injection of alpha-fluoromethylhistidine (100 microg), a selective and irreversible histidine decarboxylase 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.
Jin
Chun-Lei
CL
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
Zhuge
Zheng-Bing
ZB
Wu
Deng-Chang
DC
Zhu
Yuan-Yuan
YY
Wang
Shuang
S
Luo
Jian-Hong
JH
Chen
Zhong
Z
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D007026:Hypothalamic Area, Lateral / Q000473:pathology*; D007276:Injections, Intraventricular; D008297:Male; D008762:Methylhistidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D004791:Enzyme Inhibitors; D008762:Methylhistidines; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase; D005998:Glycine