Cold-induced thermogenesis mediated by GABA in the preoptic area of anesthetized rats.
Bilateral microinjections of GABA (300 mM, 100 nl) or the GABA(A) receptor agonist muscimol (100 microM, 100 nl) into the preoptic area (POA) of the hypothalamus increased the rate of whole body O(2) consumption (VO(2)) and the body core (colonic) temperature of urethane-chloralose-anesthetized, artificially ventilated rats. The most sensitive site was the dorsomedial POA at the level of the anterior commissure. The GABA-induced thermogenesis was accompanied by a tachycardic response and electromyographic (EMG) activity recorded from the femoral or neck muscles. Pretreatment with muscle relaxants (1 mg/kg pancuronium bromide + 4 mg/kg vecuronium bromide i.v.) prevented GABA-induced EMG activity but had no significant effect on GABA-induced thermogenesis. However, pretreatment with the beta-adrenoceptor propranolol (5 mg/kg i.v.) greatly attenuated the GABA-induced increase in VO(2) and tachycardic responses. Accordingly, the GABA-induced increase in VO(2) reflected mainly nonshivering thermogenesis. On the other hand, cooling of the shaved back of the rat by contact with a plastic bag containing 28 degrees C water also elicited thermogenic, tachycardic, and EMG responses. Bilateral microinjections of the GABA(A) receptor antagonist bicuculline (500 microM, 100 nl), but not the vehicle saline, into the POA blocked these skin cooling-induced responses. These results suggest that GABA and GABA(A) receptors in the POA mediate cold information arising from the skin for eliciting cold-induced thermogenesis.
Osaka
Toshimasa
T
National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku 162-8636, Japan. osaka@nih.go.jp
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000502:physiology*; D003080:Cold Temperature; D004576:Electromyography; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D011301:Preoptic Area / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012881:Skin Temperature / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid; D011433:Propranolol; D001640:Bicuculline