Histamine Influences Body Temperature by Acting at H1and H3 Receptors on Distinct Populations of Preoptic Neurons

Abstract

The preoptic area/anterior hypothalamus, a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular signalregulated kinase and was not dependent on synaptic activity. Furthermore, a population of non-GABAergic neurons was depolarized, and their firing rate was enhanced by histamine acting at H1 subtype receptors. In our experiments, activation of the H1R receptors was linked to the PLC pathway and Ca 2ϩ release from intracellular stores. This depolarization persisted in TTX or when fast synaptic potentials were blocked, indicating that it represents a postsynaptic effect. Single-cell reverse transcription-PCR analysis revealed expression of H3 receptors in a population of GABAergic neurons, while H1 receptors were expressed in non-GABAergic cells. Histamine applied in the median preoptic nucleus induced a robust, long-lasting hyperthermia effect that was mimicked by either H1 or H3 histamine receptor subtype-specific agonists. Our data indicate that histamine modulates the core body temperature by acting at two distinct populations of preoptic neurons that express H1 and H3 receptor subtypes, respectively.

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

“…Other antihistamine drugs such as loratadine and cyproheptadine are also associated with increased body weight and hyperplasia [70][71][72][73]. Furthermore, the H 1 R antagonistic affinity of SGAs contributes to fat accumulation via downregulation of lipolysis, while upregulating lipogenesis in white adipose tissue [74][75][76][77].…”

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

“…[19,[37][38][39] Microinjection of histamine into the PVN or preoptic area (POA), which are important regions controlling BAT thermoregulation via the sympathetic nervous system, significantly activated BAT sympathetic activity and increased BAT uncoupling protein 1 (UCP-1) mRNA expression in rats. [38] The POA, which is a main region for histamine regulating body temperature, sends outflows to the rostral raphe pallidus (rRPa) that contains sympathetic premotor neurons to regulate BAT thermogenesis (reviewed in [40] ).…”

“…Intra-MnPO (median preoptic nucleus) injection of histamine and an H1 receptor agonist, 2-pyridylethylamine, significantly induced hyperthermia without increasing motor activity in mice. [39] Studies also suggest that activation of H1 receptors expressed on glutamatergic neurons in the MnPO activates BAT thermogenesis by stimulating sympathetic neurons in the rRPa. [39,41] Additionally, in the medial preoptic nucleus (MPON), H1 receptor activation on the glutamatergic neurons also significantly regulates body temperature, although H2…”

Histaminergic Modulation of Body Temperature and Energy Expenditure

“…This finding may reflect technical limitations or the fact that PO/AH neurons send few local projections [28]. Our studies in mice have not found evidence for local projections of PO/AH GABAergic neurons but have revealed reciprocal connections of PO/AH glutamatergic neurons [21].…”

“…Recent studies have established also the existence of direct glutamatergic projections from the PO/AH [20,21] as well as from the lateral hypothalamus [22] to the rRPA that control thermoregulation. Some glutamatergic PO/AH neurons projecting to rRPa are also peptidergic [20].…”