The role of orexin-1 receptors in physiologic responses evoked by microinjection of PgE2 or muscimol into the medial preoptic area

The medial preoptic area (mPOA) of the hypothalamus has long been thought to play an important role in both fever production and thermoregulation. Microinjections of prostaglandin E2 (PgE2) or the GABAA agonist muscimol into the mPOA cause similar increases in body temperature, heart rate, and blood pressure. Microinjections of these compounds however evoke different behavioral responses with muscimol increasing and PgE2 having no effect on locomotion. The purpose of this study was to determine the role of orexin-1 receptors in mediating these dissimilar responses. Systemic injections of the orexin-1 receptor antagonist SB-334867 reduced temperature and cardiovascular responses produced by microinjections of muscimol, but had no effect on either response produced by PgE2. SB-334867 did not significantly decrease locomotion evoked by microinjections of muscimol into the mPOA. These data suggest that there are two central nervous system circuits involved in increasing body temperature, heart rate and blood pressure: one circuit activated by muscimol, involving orexin neurons, and a separate orexin-independent circuit activated by PgE2.

► mPOA microinjections of PgE2 and muscimol raise temp, HR, and MAP.
► mPOA microinjections of muscimol, but not PgE2, increase locomotion.
► SB-334867 attenuated HR, MAP, temp responses to mPOA microinjections of muscimol.
► SB-334867 had no effect on locomotor responses to microinjections of muscimol.
► SB-334867 had no effect on any responses to microinjections of PgE2.