Blockade of 5-HT2A receptors inhibits emotional hyperthermia in mice

Abstract

This study determined whether blockade of 5-hydroxytryptamine 2A (5-HT2A) receptors attenuated hyperthermia and tachycardia responses to psychological stress in mice. For this purpose, male mice (C57BL/6N) were pre-instrumented with a telemetric probe to measure core body temperature and heart rate prior to experimentation. Vehicle or 5-HT2A antagonist, eplivanserin hemifumarate (SR-46349B) ((1Z,2E)-1-(2-fluorophenyl)-3-(4-hydroxyphenyl)-2-propen-1-one O-[2-(dimethylamino) ethyl] oxime hemifumarate) (0.5, 1.0, 5.0 mg/kg), was injected intraperitoneally. To elicit psychological stress, an intruder male mouse confined to a small cage was introduced into the resident mouse’s cage 30 min after administration of the injection. The application of this psychological stress increased body temperature by\u2009~\u20091.0 °C and heart rate by\u2009~\u2009150 bpm in the vehicle group. In contrast, SR-46349B was shown to reduce this psychological stress-induced increase in body temperature in a dose-dependent manner (P\u2009<\u20090.05). However, the SR-46349B treatment groups had no influence on the intruder-elicited increase in heart rate. This study, therefore, suggests that 5-HT2A receptors play a significant role in mediating hyperthermia, but not tachycardia, during intruder-elicited psychological stress.