A dopamine-5-hydroxytryptamine link in the hypothalamic pathways which mediate heat loss in the rat

1. Intrahypothalamic injection of either dopamine or 5-hydroxytryptamine (5-HT) in a dose volume of 1 microliters caused a fall in core temperature in lightly restrained rats maintained at an ambient temperature of 17 +/- 1 degree C. 2. Haloperidol (6.5 n-mole), a dopamine antagonist, prevented the hypothermic effect of dopamine (65 n-mole), but was ineffective against the response to either intrahypothalamic 5-HT (114 n-mole) or oxotremorine (6.0 n-mole). 3. Methysergide (14 n-mole) and cryproheptadine (17 n-mole) blocked the effect of both 5-HT and dopamine. However, these same doses failed to antagonise the effect of oxotremorine. 4. Rats placed on 0.65 m below a 250 W infra-red lamp responded to the imposed heat load vasodilation of tail skin blood vessels, as indicated by an increased tail skin temperature. 5. Rats tested 2 weeks after bilateral intrahypothalamic injection of 5,6-dihydroxytryptamine (42 n-mole in 2 microliters) showed a significant reduction in their tail skin temperature response and were less able to withstand the imposed heat load. 6. 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 previously defined dopamine-sensitive site. 7. Pretreatment with 5,6-dihydroxytryptamine significantly reduced the 5-HT concentration in the dopamine sensitive site, but had no effect on the concentration of dopamine. This pretreatment blocked dopamine but not 5-HT-induced hypothermia. 8. The 5-hydroxyindoleacetic acid (5HIAA) concentration in the hypothalamus of the normal rat exposed to a heat load was found to be significantly elevated, whereas there was no change in the 5HIAA concentration in the cortex. 9. Slices of rat preoptic hypothalamus and hippocampus were incubated with [3H]5-HT (0.2-2 microM). These slices accumulated 5-HT with properties characteristic of a neuronal uptake process. 10. Perfusion with either dopamine (greater than 50 microM) or apomorphine (greater than 200 microM) enhanced the release of [3H]5-HT from the prelabelled hypothalamic slices, but failed to stimulate release from hippocampal slices. 11. The release of [3H]5-HT from preoptic slices by dopamine and apomorphine was antagonised by the dopamine antagonists haloperidol (2 microM) and (+) isomer of butaclamol (1 microM), the (-) isomer of butaclamol was inactive. 12. These results support the hypothesis of a dopamine-5HT link in the hypothalamic thermoregulatory pathways of the rat.