Histamine and Its Receptors Modulate Temperature-Preference Behaviors inDrosophila

Abstract

Temperature profoundly influences various life phenomena, and most animals have developed mechanisms to respond properly to environmental temperature fluctuations. To identify genes involved in sensing ambient temperature and in responding to its change, Ͼ27,000 independent P-element insertion mutants of Drosophila were screened. As a result, we found that defects in the genes encoding for proteins involved in histamine signaling [histidine decarboxylase (hdc), histamine-gated chloride channel subunit 1 (hisCl1), ora transientless (ort)] cause abnormal temperature preferences. The abnormal preferences shown in these mutants were restored by genetic and pharmacological rescue and could be reproduced in wild type using the histamine receptor inhibitors cimetidine and hydroxyzine. Spatial expression of these genes was observed in various brain regions including pars intercerebralis, fan-shaped body, and circadian clock neurons but not in dTRPA1-expressing neurons, an essential element for thermotaxis. We also found that the histaminergic mutants showed reduced tolerance for high temperature and enhanced tolerance for cold temperature. Together, these results suggest that histamine signaling may have important roles in modulating temperature preference and in controlling tolerance of low and high temperature.

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] ).…”

Temperature sensing across species

“…Expression of these proteins is found throughout the central nervous system but not co-expressed with dTRPA1. These mutants display a preference for warmer temperatures near 27°C, whereas wild type and rescued animals prefer to congregate near 24°C [45]. Interestingly, pharmacological antagonists of histamine receptors evoke a similar phenotype as the histaminergic mutants.…”

“…However, a recent study has uncovered a new potential player in thermosensation, histamine. Hong et al performed a P-element screen very much like that used to identify the pyrexia mutants [43], and isolated several mutants which exhibit deficits in thermotactic behaviors [45]. The genes identified encode several proteins that serve in histamine signaling, including a subunit of a histaminegated ion channel and histamine decarboxylase.…”

Glutamate-gated Chloride Channels

“…HisCls therefore play an important role in insect vision. Mutations in genes involved in histaminergic signaling, including those encoding HisCls, also affect temperature preference in the fly (80). Mutations in hclB affect not only Drosophila vision (24) but also responses to high temperature and anesthesia, suggesting a central role in the nervous system (81).…”