Dopamine in the hypothalamus of the cat: Pharmacological characterization and push-pull perfusion analysis of sites mediating hypothermia

Abstract

Within the rostral diencephalon of the cat, 113 sites were examined for their reactivity to 2.33–14.0 μg dopamine (DA) or 2.33–14.0 μg norepinephrine (NE) microinjected in a volume of 0.75 μl. During each experiment, colonic temperature was monitored and additional physiological measures were recorded continuously. In contrast to CSF controls, an intrahypothalamic injection of either catecholamine at circumscribed sites evoked a dose-dependent fall in the cat's body temperature, with NE ordinarily evoking a more profound hypothermic response. The morphological sites of maximum sensitivity were localized in the anterior hypothalamic, preoptic region. At some but not all sites, a prior microinjection of 3.5–7.0 μg phentollamine attenuated the magnitude of the DA-induced hypothermia and delayed its onset. Conversely, at all loci, the pretreatment by the injection of this alpha-adrenergic antagonist markedly reduced the absolute magnitude of the NE-induced fall in the cat's temperature. Similar pretreatment of a reactive hypothalamic locus with a beta-adrenergic receptor blocking agent, practolol (3.5 μg), failed to alter the hypothermia following a microinjection of DA. Either of two DA receptor antagonists, haloperidol (0.04–7.0 μg) or d-butaclamol (0.48–1.47 μg), when given in a sufficient dose, effictively delayed the onset of the DA-hypothermia and reduced its absolute magnitude; however, the NE-induced decline in the cat's temperature was unaffected by DA receptor blockade. Endogenous stores of DA and/or NE in the cat's hypothalamus were radio-labeled with either 3H- or 14C-catecholamines or both, microinjected through the implanted guide tube into an identified amine-sensitive site. By using push-pull cannulae, the site was subsequently perfused for 5 min with artificial CSF at a rate of 25 μl/min with samples collected at 15 min intervals. During either the third or fourth perfusion, the ambient temperature of the cat's chamber of 22–24°C was elevated to 35–45°C and maintained at this level for 15 or 30 min. This environmental warming evoked a release of either DA or NE or both amines from certain circumscribed sites within the cat's rosrtal hypothalamus. Overall, these results provide pharmacological, physiological and anatomical evidence for a differential role of DA in the hypothalamic mechanism which mediates the heat loss processes.