Cold-induced thermogenesis mediated by GABA in the preoptic area of anesthetized rats

Abstract

Bilateral microinjections of GABA (300 mM, 100 nl) or the GABA_Areceptor agonist muscimol (100 μM, 100 nl) into the preoptic area (POA) of the hypothalamus increased the rate of whole body O₂consumption (V̇o₂) 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 iv) prevented GABA-induced EMG activity but had no significant effect on GABA-induced thermogenesis. However, pretreatment with the β-adrenoceptor propranolol (5 mg/kg iv) greatly attenuated the GABA-induced increase in V̇o₂and tachycardic responses. Accordingly, the GABA-induced increase in V̇o₂reflected mainly nonshivering thermogenesis. On the other hand, cooling of the shaved back of the rat by contact with a plastic bag containing 28°C water also elicited thermogenic, tachycardic, and EMG responses. Bilateral microinjections of the GABA_Areceptor antagonist bicuculline (500 μM, 100 nl), but not the vehicle saline, into the POA blocked these skin cooling-induced responses. These results suggest that GABA and GABA_Areceptors in the POA mediate cold information arising from the skin for eliciting cold-induced thermogenesis.