Blockade of prostaglandin E 2-induced thermogenesis by unilateral microinjection of GABA A receptor antagonist into the preoptic area

Abstract

Previous studies have demonstrated that pretreatment of rats with a GABA A receptor antagonist microinjected bilaterally into the preoptic area (POA) blocked cold- or lipopolysaccharide-induced thermogenesis. Here, the involvement of GABA A receptors in prostaglandin (PG)E 2-induced fever was examined. Thermogenic, tachycardic, vasoconstrictive, and hyperthermic responses were elicited by the unilateral microinjection of 0.57–1.1 pmol PGE 2 into the region adjacent to the organum vasculosum of the lamina terminalis in urethane–chloralose-anesthetized rats. All these responses were blocked 10 min after pretreatment of the rats with a GABA A receptor antagonist, bicuculline methiodide or gabazine (50–500 pmol), microinjected unilaterally into the POA; and recovery occurred at ∼ 70 min. Though the antagonist treatment alone had no effect on the O 2 consumption rate or colonic temperature, it did elicit a bradycardic response. Pretreatment with the vehicle, saline, had no effect on the PGE 2-induced responses. However, the blocking action of bicuculline/gabazine was efficacious when the agent was administered unilaterally, but not necessarily bilaterally, into the POA either contralateral or ipsilateral to the PGE 2 injection site. These results suggest that the PGE 2-induced responses are not simply mediated by the GABAergic transmission from the PGE 2-sensitive site to the thermoefferent structure in the POA, although a tonic inhibitory input to POA neurons has a permissive role for the full expression of PGE 2-induced fever.