Further evidence for a physiological role for hypothalamic dopamine in thermoregulation in the rat

1. Intrahypothalamic injection of either dopamine or noradrenaline in a dose volume of 1 mul. caused a fall in core temperature in lightly restrained rats maintained at an ambient temperature of 17 +/- 1 degrees C.2. The hypothermic effects of dopamine (10 mug) and noradrenaline (2 mug) were selectively antagonized by systemic pre-treatment with pimozide (0.5 mg/kg) and phentolamine (1 mg/kg) respectively.3. The location of the dopamine- and noradrenaline-sensitive sites were defined more accurately by reducing the dose volume to 0.5 mul. and making injections at different points throughout the preoptic region.4. Both the dopamine- and the noradrenaline-sensitive sites were located within the preoptic region, but they did not have identical locations being separated by a distance of 0.4 mm.5. Unilateral intrahypothalamic injection of 6-hydroxydopamine (10 mug in 2 mul.) caused a significant fall in core temperature, which was antagonized by systemic injection of either pimozide or phentolamine.6. Rats placed 0.65 m below a 250 W infra-red lamp responded to the imposed heat load by vasodilation of tail skin blood vessels, indicated by an increased tail skin temperature.7. Rats were tested two weeks after bilateral intrahypothalamic injection of 6-hydroxydopamine (10 mug in 2 mul.). This pre-treatment significantly reduced the increase in tail skin temperature so that the rats were less able to withstand the imposed heat load. Rats receiving similar 6-hydroxydopamine pre-treatment following injection of desipramine (25 mg/kg, I.P.) were also less able to cope with a heat load.8. Three serial sections (0.8 mm thick) were prepared from the preoptic area of the rat brain, one anterior, one posterior and one corresponding to the dopamine-sensitive site.9. Pre-treatment with 6-hydroxydopamine reduced both the dopamine and the noradrenaline concentration in the dopamine-sensitive site. Pre-treatment with desipramine and 6-hydroxydopamine selectively reduced dopamine.10. These results indicate that there are receptors for both dopamine and noradrenaline in the preoptic anterior hypothalamus, which mediate a fall in core temperature in rats, but the evidence suggests that it is endogenous dopamine which is more likely to play an important physiological role.