The effects of theophylline and caffeine on thermoregulatory functions of rats at different ambient temperatures

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Abstract
Both systemic and central administration of theophylline and caffeine produced a dose-dependent rise in rectal temperature at ambient temperatures of 8, 22 and 30°C. The hyperthermia in response to either xanthine was brought about by an increase in metabolic heat production. In addition, their administration produced behavioral excitation, cutaneous vasodilation (as estimated by an increase in the foot and tail skin temperatures) and diuresis. There was no change in respiratory evaporative heat loss. Probably, the hyperthermia induced by the two drugs was due to behavioral excitation leading to an increased metabolism at the ambient temperatures studied. Furthermore, either destruction of central catecholaminergic nerve fibres (with 6-hydroxydopamine) or blockade of α-adrenergic and dopaminergic (with phentolamine and haloperidol) receptors antagonized the xanthine-induced hyperthermia. The data suggest that these xanthines elicit a central activation of both adrenergic and dopaminergic receptors via release of endogenous catecholamines that leads to behavioral excitation and hyperthermia in rats.