Co-existence of H1 and H2 histaminergic receptors in individual neurons of rat hypothalamic ventromedial nucleus (VMN)

Histamine is a ubiquitous brain neurotransmitter. Estrogen hormones have been shown to increase histamine effects on neurons located in the ventromedial nucleus of the hypothalamus (VMN) (Kow et al, 2005a). This study has been set up to find candidate pathways to explain the mechanism(s) by which estradiol does this enhancement. Therefore, we decided to look at which histamine receptors are involved in histamine-induced depolarization. Previous studies (Zhou et al, 2007) showed that in mice only the histamine receptor H1 (H1-R) is involved in histamine actions on VMN neurons. It seems however that in rats the mechanism includes more than one receptor. By using histamine agonists (betahistidine and dimaprit) in whole cell patch clamp experiments we revealed that both H1-R and histamine receptor H2 (H2-R) coexist and can mediate opposite actions of histamine on individual VMN neurons. To refine our pharmacological study histamine antagonists were used too. The blocking of both these two receptors revealed that a histamine response is the sum of the depolarization and hyperpolarization by H1-R and H2-R, respectively. Colocalization of H1-R and H2-R on the same cells was therefore suggested and will be evaluated by Immunohistochemistry.