The histaminergic system is involved in psychological stress‐induced hyperthermia in rats

The histaminergic system modulates numerous physiological functions such as wakefulness, circadian rhythm, feeding, and thermoregulation. However, it is not yet known if this system is also involved in psychological stress‐induced hyperthermia (PSH) and, if so, which histamine (H) receptor subtype mediates the effect. Therefore, we investigated the effects of pretreatments with intraperitoneal injections of mepyramine (an H1 receptor inverse agonist), cimetidine (an H2 receptor antagonist), and ciproxifan (an H3 receptor inverse agonist) on cage‐exchange stress‐induced hyperthermia (a model of PSH) by monitoring core body temperature (T (c)) during both light (10:00 am–12:00 pm) and dark (10:00 pm–12:00 am) phases in conscious, freely moving rats. We also investigated the effects of these drugs on stress‐induced changes in locomotor activity (L (a)) to rule out the possibility that effects on T (c) are achieved secondary to altered L (a). Cage‐exchange stress increased T (c) within 20 min followed by a gradual decrease back to baseline T (c) during both phases. In the light phase, mepyramine and cimetidine markedly attenuated PSH, whereas ciproxifan did not affect it. In contrast, in the dark phase, mepyramine dropped T (c) by 1°C without affecting cage‐exchange stress‐induced hyperthermia, whereas cimetidine and ciproxifan did not affect both postinjection T (c) and PSH. Cage‐exchange stress induced an increase in L (a), especially in the light phase, but none of these drugs altered cage‐exchange stress‐induced L (a) in either circadian rhythm phase. These results suggest that the histaminergic system is involved in the physiological mechanisms underlying PSH, particularly through H1 and H2 receptors, without influencing locomotor activity.