4. Histamine and its receptors in animal studies for epilepsy
There are many limitations to clinical researches. Animal models of
epileptic seizures have an indispensable role in the advancement of
investigating the causal role of histamine and its receptor in epilepsy,
have been instrumental in the preclinical development of new
antiepileptic agents. The models of epilepsy or seizures can be
classified into genetic animal models and acquired animal models. For
the former, it includes transgenic mice with spontaneous recurrent
seizures, and animals with reflex seizure, such as DBA/2 mice, GEPR, and
Krushinski-Molodkina (KM) animals. For the latter, there are usually two
common ways to induce seizures in normal animals:
electrical
induction and chemical induction.
Pentylenetetrazole
(PTZ), pilocarpine (Ach M receptor agonist),
strychnine
(STR),
kainic
acid (KA, glutamate receptors agonists), and picrotoxin
(GABAA receptor antagonist) are commonly used chemical
substance to induce seizure. Maximal electroshock seizure (MES),
amygdaloid kindling, 6-Hz stimulation and transauricular kindling are
commonly used as electrical induction method of seizure. Besides, except
for the electrical and chemical indication of seizures in normal
animals, there are other seizure-induced models, such as audiogenic
stimulation, vestibular stimulation and hyperthermia-induced febrile
seizure (Löscher, 2011; Potschka, 2012). Actually, the electrical and
chemical induction methods are combined use together in some cases.
Next, we summarize findings of changes in histamine level or histamine
receptor expression in across chemically and electrically-induced
epilepsy animal models, as well as other animal models (Table 2).
Moreover, we also pay attention to review the therapeutic effect of
histamine or histamine receptors related ligands on epilepsy (Table 3),
and genetic interventions, especially genetic-edited animal, as well as
other interventions in epilepsy in animal researches. The change of
histamine and histamine receptor and the therapeutics effect of
histamine related ligands in epilepsy are showed in Fig.2.