Control of body temperature in the unanaesthetized monkey by cholinergic and aminergic systems in the hypothalamus

In the conscious monkey (Macaca cyclopis) intravenous administration of chlorpromazine 0.1–8.0 mg/kg produced a fall of rectal temperature of 0.3 to 3.5°C after a latency of 3.5 to 10.8 minutes. The course of hypothermia lasted from 125 to 600 min or more. Direct injection of chlorpromazine 100–800 μg into the lateral or fourth cerebral ventricle produced a similar fall of 0.3 to 2.0°C but with shorter latency (2 to 3.5 min) and with a duration of 94 to 375 minutes. Two distinct structures in the brain stem, namely, the preoptic anterior hypothalamus (POAH) and medulla oblongata, responded to direct injection of chlorpromazine 200 μg. The sensitivity was slightly higher in the POAH than in the medulla. Structures in between were not sensitive. The results suggest that chlorpromazine works principally through the central nervous system, i.e. the POAH and medulla oblongata, to mediate its hypothermic effect.

Section: Methodsmentioning

confidence: 99%

Section: General Reactions After Administration Of Chlorpromazinementioning

confidence: 99%

Hypothermic Action of Chlorpromazine in Monkeys

Chai

Fann

Lin

1976

“…Intraventricularly or intrahypothalamically injected 5-hydroxytryptamine and acetylcholine produce hyperthermia (Feldberg et al, 1967;Myers & Yaksh, 1969). However, the possibility that the GABA-induced hyperthermia is mediated by 5-hydroxytryptamine or acetylcholine is excluded because of (1) the increased hyperthermic response observed with GABA in dogs treated with reserpine which is known to deplete brain 5-hydroxytryptamine (Pletscher, Shore & Brodie, 1956); (2) the inability of BOL, which blocks brain tryptamine receptors (Tedeschi, Tedeschi & Fellows, 1959), and of hyoscine, a drug closely allied to atropine which blocks the hyperthermic effects of intraventricularly injected carbachol (Hall, 1972), to antagonize GABA-induced hyperthermia; and (3) the failure of GABA to release 5-hydroxytryptamine or acetylcholine into the effluent.…”

Section: Drugsmentioning

confidence: 99%

“…The effects on body temperature of intraventricularly or intrahypothalamically injected noradrenaline and adrenaline, 5-hydroxytryptamine, acetylcholine and PGE1 have been extensively investigated in several species of animals (Feldberg & Myers, 1963, 1964a, 1964b, 1965Feldberg, Hellon & Lotti, 1967;Myers, 1967;Cooper, Granston & Honour, 1965;Bligh, 1966;Findlay & Robertshaw, 1967;Anderson, Jobin & Olsson, 1966;Brittain & Handley, 1967;Myers & Yaksh, 1969;Feldberg & Saxena, 1971a, 1971bMilton & Wendlandt, 1971).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Effects on Body Temperature of Intracerebroventricular Injection in Anaesthetized Dogs of Gamma‐aminobutyric Acid

Dhumal

Gulati

Raghunath

et al. 1974

1 The cerebral ventricles of dogs under intravenous pentobarbitone sodium anaesthesia, were perfused with artificial cerebro-spinal fluid (CSF) at a rate of 0.4-0.5 ml/min from the ventricular to the aqueductal cannulae. The effluent was collected from the aqueductal cannula in 20 min samples. The animals' temperatures were recorded from the rectum.2 y-Aminobutyric acid (GABA) 0.1-5 mg when injected into the ventricles produced variable temperature effects. Doses of 0.1 and 0.5 mg always produced hyperthermia and 1 and 5 mg doses sometimes produced hyperthermia and sometimes hypothermia. 3 Intraventricular perfusion with 2-bromolysergic acid diethylamide (BOL) and hyoscine did not block hyperthermia. Tests on the rat isolated stomach strip or the guinea-pig isolated superfused ileum for the possible release, respectively, of 5-hydroxytryptamine or acetylcholine by GABA were negative. 4 When tested for the presence of prostaglandin E(PGE)-like substances on the isolated rat stomach strip, both the control effluent and the GABA effluent showed activity, the latter being much more potent. There was a temporal correlation between this effect and hyperthermia. Intraventricularly administered sodium salicylate converted the GABA-induced hyperthermia to hypothermia and blocked the release of PGE-like substances. 5Hypothermia induced by GABA alone or in the presence of sodium salicylate was associated with the release of noradrenaline into the effluent. 6 Intraventricular administration of GABA in reserpinized dogs produced hyperthermia and not hypothermia. Similar results were obtained with phentolamine perfusion in normal dogs. 7 Perfusion with calcium-free solution blocked both the noradrenaline-releasing and hypothermic actions of GABA. 8 It is concluded that hyperthermia associated with intraventricular injections of GABA is due to the release of PGE-like substance and hypothermia is due to the release of noradrenaline.

“…By means of micro-injection techniques in primates, Myers and his co-workers have mapped out areas of the diencephalon most sensitive to cholinergic stimulation using carbachol (Myers & Yaksh, 1969) and later nicotine (Hall & Myers, 1971). Briefly, these workers found that whilst both drugs produced hyperthermia when injected into the posterior hypothalamus only carbachol did so when injected into the anterior hypothalamus and preoptic area.…”

Section: Introductionmentioning

confidence: 99%

Temperature and Behavioural Responses Induced in the Unanaesthetized Cat by the Central Administration of Rx72601, a New Anticholinesterase

Metcalf

Myers

Redgrave

1975

The central effects produced by a new anticholinesterase RX72601 injected into the cerebral ventricles or perfused within circumscribed forebrain structures have been investigated in the unanaesthetized cat. When injected into the cerebral ventricles in doses of 1–10 μg, RX72601 produced a dose‐related hyperthermia together with behavioural and autonomic responses. Experiments designed to localize the site or sites of these actions demonstrated that hyperthermia could be produced from several diencephalic sites but that the other effects were not normally produced from these same sites.