Mechanism of H2 histamine receptor dependent modulation of body temperature and neuronal activity in the medial preoptic nucleus

Abstract

Histamine is involved in the central control of arousal, circadian rhythms and metabolism. The preoptic area, a region that contains thermoregulatory neurons is the main locus of histamine modulation of body temperature. Here we report that in mice histamine activates H2 subtype receptors in the medial preoptic nucleus (MPON) and induces hyperthermia. We also found that a population of glutamatergic MPON neurons express H2 receptors and are excited by histamine or H2 specific agonists. The agonists decreased the input resistance of the neuron and increased the depolarizing “sag” observed during hyperpolarizing current injections. Furthermore, at −60 mV holding potential activation of H2 receptors induced an inward current that was blocked by ZD7288, a specific blocker of the hyperpolarization activated cationic current (Ih). Indeed, activation of H2 receptors resulted in increased Ih amplitude in response to hyperpolarizing voltage steps and a depolarizing shift in its voltage-dependent activation. The neurons excited by H2 specific agonism expressed the HCN1 and HCN2 channel subunits. Our data indicate that at the level of the MPON histamine influences thermoregulation by increasing the firing rate of glutamatergic neurons that express H2 receptors.

The Role of Hypothalamic H1 Receptor Antagonism in Antipsychotic-Induced Weight Gain

“…[42] Furthermore, a body of evidence has shown the importance of the PVN in central regulation of BAT sympathetic activity and energy expenditure (reviewed in [43] ). The PVN contains thermoregulatory neurons which project to the rRPa and rostral ventrolateral medulla (rVLM), important autonomic regions, to regulate sympathetic outflows to BAT and contributes to BAT thermoregulation.…”

Histaminergic Modulation of Body Temperature and Energy Expenditure

“…Histamine activates H2 subtype receptors in the MPON and induces hyperthermia [60]. We also found that a population of glutamatergic MPON neurons express H2Rs and are excited by H2R specific agonists.…”

“…The neurons excited by H2 specific agonism expressed the HCN1 and HCN2 channel subunits. Our data indicate that at the level of the MPON histamine influences thermoregulation by increasing the firing rate of glutamatergic neurons that express H2Rs [60]. …”

“…In contrast, H2R specific agonists mimicked the histamine effect when administered intra-MPON, while H1R specific agonists had little effect [60]. Surprisingly, H3R specific agonists were without effect in this nucleus [60].…”

“…H1R and H3R specific agonists were equally potent in inducing a hyperthermia when infused in the median preoptic nucleus [21]. In contrast, H2R specific agonists mimicked the histamine effect when administered intra-MPON, while H1R specific agonists had little effect [60]. Surprisingly, H3R specific agonists were without effect in this nucleus [60].…”