Blockade of prostaglandin E2-induced thermogenesis by unilateral microinjection of GABAA receptor antagonist into the preoptic area.
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)E2-induced fever was examined. Thermogenic, tachycardic, vasoconstrictive, and hyperthermic responses were elicited by the unilateral microinjection of 0.57-1.1 pmol PGE2 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 approximately 70 min. Though the antagonist treatment alone had no effect on the O2 consumption rate or colonic temperature, it did elicit a bradycardic response. Pretreatment with the vehicle, saline, had no effect on the PGE2-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 PGE2 injection site. These results suggest that the PGE2-induced responses are not simply mediated by the GABAergic transmission from the PGE2-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 PGE2-induced fever.
Osaka
Toshimasa
T
National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku 162-8636, Japan. osaka@nih.go.jp
D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced; D007839:Functional Laterality / Q000502:physiology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D008297:Male; D008845:Microinjections; D010101:Oxygen Consumption / Q000187:drug effects; D011301:Preoptic Area / Q000502:physiology*; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D022722:Thermogenesis / Q000187:drug effects*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011724:Pyridazines; C049853:gabazine; D015232:Dinoprostone; D001640:Bicuculline