Do adenosine antagonists improve cold tolerance by reducing hypothalamic adenosine activity in rats?

Previously we have shown that systemic injection of adenosine antagonists can significantly improve cold tolerance in both rats and humans. However, it is not clear whether systemic administration of adenosine antagonist acts peripherally or centrally at the thermoregulatory site. To resolve this, theophylline (nonselective adenosine receptor blocker), cyclopentyltheophylline (selective A1 receptor blocker) or adenosine deaminase (an enzyme which inactivates adenosine by converting it into inosine) was injected directly into preoptic anterior hypothalamus (POAH) of rats and their thermogenic responses assessed. In contrast to that observed after systemic administration, intrahypothalamic injection of either adenosine antagonists or deaminase at various doses failed to elicit any enhancement in heat production beyond that of the controls. These results suggest that the beneficial effect of systemically injected adenosine antagonists in improving cold tolerance is not the result of altering the thermoregulatory functions mediated via the POAH.