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579232 
Journal Article 
Effects of the 5-HT2A antagonist mirtazapine in rat models of thermoregulation 
Pawlyk, AC; Cosmi, S; Alfinito, PD; Maswood, N; Deecher, DC 
2006 
Yes 
Brain Research
ISSN: 0006-8993
EISSN: 1872-6240 
1123 
1 
135-144 
English 
17067560 
Thermoregulation is a complex intercommunicative function requiring coordination between core body temperature (CBT), the central nervous system, and peripheral vasculature. In menopausal women, dysregulation of thermoregulatory mechanisms leads to hot flushes and night sweats. A previous study in ovariectomized (OVX) rats has suggested that mirtazapine can alleviate thermoregulatory dysfunction by blocking 5-HT2A receptor signaling. This is in opposition to other work in which 5-HT2A receptor blockade appeared to exacerbate thermoregulatory dysfunction in OVX rats. Thus, the goals of the present study were to reexamine the effects of mirtazapine on temperature regulation in OVX rat models and explore further the role of 5-HT2A receptor blockade. Mirtazapine exhibited potent functional antagonism (EC50 = 0.62 nM) at the cloned human 5-HT2A receptor. In the morphine-dependent model of thermoregulatory dysfunction, mirtazapine (10 mg/kg, i.p.) induced an increase in tail-skin temperature (TST) prior to naloxone administration. In the telemetry model, mirtazapine (0.3-3 mg/kg, i.p.) caused an increase in TST. However, at the highest dose tested (10 mg/kg, i.p.), mirtazapine induced a small but significant decrease in TST followed by an increase in TST. To examine this finding further, mirtazapine's effect on CBT was determined. Administration of mirtazapine (1-3 mg/kg, i.p.) resulted in a slight decrease in CBT but at the 10 mg/kg dose a dramatic decrease (- 3.6 °C) in CBT was observed. These data support the concept that 5-HT2A receptors play a role in temperature regulation but that functional blockade of these receptors by mirtazapine is not a likely mechanism for restoring thermoregulatory processes in OVX rats. 
Thermoregulation; Vasomotor symptom; 5-HT2A receptor; Hot flush; Rat model; Mirtazapine