Prostaglandin E2 fever mediated by inhibition of the GABAergic transmission in the region immediately adjacent to the organum vasculosum of the lamina terminalis

Unilateral microinjection of prostaglandin (PG)E2 into a region immediately adjacent to the organum vasculosum of the lamina terminalis (peri-OVLT) in the preoptic area elicited thermogenic, tachycardic, cutaneous vasoconstrictive, and hyperthermic responses simultaneously in urethane–chloralose-anesthetized rats. The magnitude of these responses increased dose-dependently over the range of 57 fmol–2.8 pmol, except for the vasoconstrictive response. Microinjection of a GABAA receptor antagonist, bicuculline methiodide or gabazine (5–20 pmol), into the PGE2-sensitive site in the peri-OVLT region also elicited responses similar to those induced by PGE2. Although administration of a GABAA receptor agonist, muscimol (10 pmol), microinjected into the same site alone usually had no effect on the rate of whole-body O2 consumption, heart rate or colon and skin temperatures, all PGE2-induced responses were blocked 10 min after the muscimol pretreatment and recovered at 50–90 min. Pretreatment with the vehicle, saline, had no effect on the PGE2-induced responses. These results suggest that spontaneous release of GABA and tonic activation of GABAA receptors in the peri-OVLT region prevent the elevation in the body core temperature under normal circumstances and that PGE2-induced febrile responses are mediated, at least in part, by inhibition of the GABAergic transmission in this area.