2-Deoxy-d-glucose-induced hypothermia in anesthetized rats: Lack of forebrain contribution and critical involvement of the rostral raphe/parapyramidal regions of the medulla oblongata

• Systemic administration of 2-deoxy-d-glucose (2DG) produces glucoprivation in cells.
• The 2DG treatment elicited heat loss and hypothermia in anesthetized rats.
• The rate of heat production was not changed significantly by the 2DG treatment.
• Decerebration had no effect on the 2DG-induced hypothermic responses.
• The responses were mediated by GABAergic transmission in the ventromedial medulla.

Systemic or central administration of 2-deoxy-d-glucose (2DG), a competitive inhibitor of glucose utilization, induces hypothermia in awake animals and humans. This response is mediated by the central nervous system, though the neural mechanism involved is largely unknown. In this study, I examined possible involvement of the forebrain, which contains the hypothalamic thermoregulatory center, and the medullary rostral raphe/parapyramidal regions (rRPa/PPy), which mediate hypoxia-induced heat-loss responses, in 2DG-induced hypothermia in urethane–chloralose-anesthetized, neuromuscularly blocked, artificially ventilated rats. The intravenous injection of 2DG (250 mg kg−1) elicited an increase in tail skin temperature and decreases in body core temperature and the respiratory exchange ratio, though it did not induce any significant change in the metabolic rate. These results indicate that the hypothermic response was caused by an increase in heat loss, but not by a decrease in heat production and that it was accompanied by a decrease in carbohydrate utilization and/or an increase in lipid utilization as energy substrates. Complete surgical transection of the brainstem between the hypothalamus and the midbrain had no effect on the 2DG-induced hypothermic responses, suggesting that the hindbrain, but not the forebrain, was sufficient for the responses. However, pretreatment of the rRPa/PPy with the GABAA receptor blocker bicuculline methiodide, but not with vehicle saline, greatly attenuated the 2DG-induced responses, suggesting that the 2DG-induced hypothermia was mediated, at least in part, by GABAergic neurons in the hindbrain and activation of GABAA receptors on cutaneous sympathetic premotor neurons in the rRPa/PPy.