Comparison of the effects of local hypothalamic acetylcholine and RF-heating on non-shivering thermogenesis in the guinea pig

Surprisingly the first reports of the effect of cholinomimetic drugs on body temperature concerned experiments in man. In 1931, Harvey Cushing and, several y ears later, Henderson and Wilson {1936), observed profuse sweating, decreased metabolic rate and dramatic fall in rectal temperature in patients a fter intraventricular injection of pilocarpine and acetylcholine (ACh). Since then, there have been numerous studies, recently reviewed by Lomax (1970), indicating that eho]inergic agents cause, in most cases, a fall in body temperature. The available evidence suggests that this is due to a direct action on the thermoregulatory centres in the rostral hypothalamus. Since cholinergic stimulation leads to a fall in temperature, either the preoptic thermosensitive s tructures stimulating heat loss and inhibiting heat production may be cholinergic in nature, or else the cholinergic synapses may be involved in the setting of the thermostat, specifically in the decreasing of the set point. In order to find out which of the two conceivable structures is responsible for the observed temperature changes, and which peripheral mechanisms participate in this thermoregulatory reaction, the following experiments in guinea pigs were made. METHODS By means of chronically implanted cannulas, thermocouples and heating electrodes in two different frontal planes of the forebrain (3 mm apart) we were able, using young nonanaesthetized animals, either to inject small amounts of biogenic amine or to change the temperature locally in the respective plane. The oxygen uptake as a measure of nonshivering thermogenesis (NST), the integrated electrical muscle activity as a measure of shivering and a number of different body temperatures were continually recorded. It was possible, through local radiofrequency (RF) heating, to reduce substantially the cold induced NST, i.e. by more than 50%, from only one of the two planes. The area containing the warm sensitive units responsible for the control of NST was identified as the preoptic area. The temperature in the locally heated areas never exceeded 43°C in these experiments. Acetylcholine combined with neostigmine (0.25 V g) in a dose of 5 ~g or carbachol in a dose of 0.25 vg were then injected in a constant injection volume of 1 ~1 in the respective planes. Both substances had similar effects, but carbachol produced somewhat more pronounced responses. The effects of local l~ypothalamic ACh-injection and of RF-heating on the cold induced NST were then compared in the two forebrain planes. For more details on the methods see Zeisberger and Briick (1971a).