Neuroanatomical mapping of hypothalamic regions mediating verapamil hyper- and hypothermia in the cat

Guide cannulae for microinjection and push-pull perfusion in the unrestrained cat were implanted bilaterally in the anterior hypothalamic, preoptic area (AH/POA) and posterior hypothalamus (PH). Postoperatively, the region was first identified in AH/POA which was reactive to norepinephrine or in PH to excess Ca++ ions; in both cases a hypothermic response was produced. Then either an artificial CSF control vehicle or the Ca++ ion channel blocking agent, verapamil, was perfused for 30 min by means of push-pull cannulae at a rate of 25.0 microliters/min. Verapamil 0.4, 2.0 and 4.0 micrograms/microliter) induced a concentration-dependent hypothermia when perfused within AH/POA sites but hyperthermia when perfused in the caudal hypothalamus. An anatomical analysis of the sites of perfusion revealed that verapamil's thermolytic effect was localized within the classical thermosensitive region of the cat's diencephalon, a region ventral to the anterior commissure and dorsal to the optic chiasm. On the other hand, the loci in which verapamil evoked thermogenesis were localized to a region dorsal to the mammillary bodies and caudal to the descending columns of the fornix. It is suggested that verapamil interferes with Ca++ ion channels in the PH to shift the cat's "set-point" temperature. Conversely, however, verapamil apparently could act on catecholaminergic terminals in AH/POA to enhance the presynaptic release of norepinephrine which, in turn, stimulates the heat loss pathway to yield hypothermia.