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.