Effects of the 5-HT2A antagonist mirtazapine in rat models of thermoregulation.

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Pawlyk AC, Cosmi S, Alfinito PD, Maswood N, Deecher DC

Effects of the 5-HT2A antagonist mirtazapine in rat models of thermoregulation.

Brain Res. 2006 Dec 6;1123(1):135-44. doi: 10.1016/j.brainres.2006.09.050. Epub 2006 Oct 24.

PubMed ID

17067560 [ View in PubMed

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Abstract

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-HT(2A) receptor signaling. This is in opposition to other work in which 5-HT(2A) 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-HT(2A) receptor blockade. Mirtazapine exhibited potent functional antagonism (EC(50)=0.62 nM) at the cloned human 5-HT(2A) 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 degrees C) in CBT was observed. These data support the concept that 5-HT(2A) 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Mirtazapine	5-hydroxytryptamine receptor 2A	Protein	Humans	Yes	Antagonist	Details