Body temperature responses in cats and rabbits to the monoamine oxidase inhibitor tranylcypromine

1. In unanaesthetized cats tranylcypromine (1-10 mg/kg) had scarcely any effect on rectal temperature when injected intraperitoneally, yet such injections prevented the deep and long-lasting fall in rectal temperature which normally occurs when the cat is anaesthetized by intraperitoneal pentobarbitone sodium or intravenous chloralose. The anaesthesia itself, however, was not affected. In some of the experiments with pentobarbitone sodium rectal temperature even rose to fever level.2. In anaesthetized as well as in unanaesthetized cats injections of tranylcypromine (0.1-1 mg) into the cerebral ventricles caused a rise in rectal temperature.3. In rabbits, rectal temperature was scarcely affected when surgical anaesthesia was produced by intravenous infusions of pentobarbitone sodium under the same condition in which, in cats, intraperitoneal pentobarbitone sodium produced a deep and long-lasting fall in temperature, i.e. when no external heat was applied but excessive dissipation of heat was prevented by placing the rabbit on a cotton-wool pad. However, when it was placed on the metal surface of an operating table, the anaesthesia was associated with a deep fall in rectal temperature.5. In anaesthetized and unanaesthetized rabbits tranylcypromine had no effect on rectal temperature when injected intraperitoneally (10 mg/kg) or into the cerebral ventricles (1 mg).5. These results are discussed in relation to the theory that the three monoamines in the hypothalamus, 5-hydroxytryptamine (5-HT), adrenaline and noradrenaline, act as central transmitters in temperature regulation.     

Effects on temperature of monoamines injected into the cerebral ventricles of anaesthetized dogs

1. In dogs anaesthetized with pentobarbitone sodium an injection of adrenaline or noradrenaline into the cerebral ventricles through a cannula implanted into the left lateral ventricle caused a fall in rectal temperature as a result of cessation of shivering, loss of muscle tone, and skin vasodilatation. 5-Hydroxytryptamine (5-HT) similarly applied caused shivering and a rise in rectal temperature.2. The hypothalamus of the dog thus appears to react to the three monoamines in the same way as in the cat, and not as in the rabbit and sheep.     

The effect of stress on the concentration of 3beta-hydroxypregn-5-en-20-one (pregnenolone) and pregn-4-ene-3,20-dione (progesterone) in the adrenal gland of the rat

1. In cats anaesthetized with pentobarbitone sodium the third ventricle was perfused with artificial c.s.f., the effluent was collected in 30 min samples and assayed for 5-hydroxytryptamine (5-HT) on the rat stomach-strip preparation. Rectal temperature was monitored continuously.2. On perfusion of artificial c.s.f. through the third ventricle, small amounts of 5-HT appeared in the effluent; the amounts decreased with successive samples.3. When tranylcypromine (Parnate), an inhibitor of amine oxidase, was added to the perfusion fluid and perfusion was continued, the 5-HT output increased. This increase was associated with shivering and a rise in temperature which was not, however, maintained.4. When tranylcypromine was injected intraperitoneally, during the fall in temperature produced by the pentobarbitone sodium anaesthesia, the 5-HT output also increased, shivering occurred and the fall in temperature was halted or reversed. The effect on temperature was maintained.5. When the cat was killed and perfusion was continued, the 5-HT output, already elevated by the tranylcypromine before death, increased even further in the next few samples.     

Synaptic stimulation superimposed on motoneurones firing in the `secondary range' to injected current

1. In cats anaesthetized with intraperitoneal pentobarbitone sodium the third ventricle, the anterior or inferior horn of the left lateral ventricle, was perfused with 5-hydroxytryptophan (5-HTP) in different concentrations, and the effluent assayed for 5-hydroxytryptamine (5-HT) on the rat stomach strip preparation of Vane (1957).2. On perfusion of the third ventricle with 5-HTP the output of 5-HT in effluent increased, the increase depending on the 5-HTP concentration: with 1/50,000 it increased 44-69 times (mean 55), with 1/25,000, 81-83 times (mean 82) and with 1/10,000, 71-200 times (mean 128). The 5-HT output depended also on the initial output during the preceding perfusion with artificial c.s.f. The greater this initial output the greater was the maximum output reached during the 5-HTP perfusion.3. The increase in 5-HT output during perfusion of the third ventricle with 5-HTP was usually associated with shivering and a rise in rectal temperature. This association, however, was not invariably obtained, probably because of a central depressant effect of 5-HTP itself.4. On perfusion of the anterior or inferior horn of the left lateral ventricle with 5-HTP, the output of 5-HT in the effluent also increased, but to a lesser extent than in the effluent from the third ventricle. There was no association with shivering nor with a rise in rectal temperature.5. An injection of 1 or 2 mg 5-HTP into the cerebral ventricles of unanaesthetized cats produced a biphasic rise in temperature, shivering, constriction of the skin vessels followed by vasodilatation, tachypnoea, wiping and scratching movements, miaowing and long lasting sleep.6. The biphasic rise in temperature is explained as the result of two opposing effects: increased formation of 5-HT which would raise body temperature, and a central depressant effect of 5-HTP itself or of one of its metabolites which would lower body temperature.7. The initial rise in temperature and the shivering in response to an intraventricular injection of 5-HTP varied from cat to cat. In those in which these effects were strong the 5-HT output during a subsequent perfusion of the third ventricle with artificial c.s.f. was higher, and the maximum 5-HT output reached on perfusion with 5-HTP was greater than in those in which these effects had been weak.     

Appearance of 5-hydroxytryptamine and an unidentified pharmacologically active lipid acid in effluent from perfused cerebral ventricles

1. In cats anaesthetized with intraperitoneal pentobarbitone sodium, three regions of the cerebral ventricles, the third ventricle, the inferior or the anterior horn, were perfused with artificial c.s.f. and the effluent was tested on the fundus strip of the rat's stomach.2. Effluent from all three regions contracted the fundus strip. The contractions were due to at least two substances as revealed by treatment of the strip with 2-bromolysergic acid diethylamide (BOL). The contractions that were sensitive to BOL are attributed to 5-hydroxytryptamine (5-HT) whereas the BOL resistant contractions appear to be due to an unknown hydroxy acid related to irin or the prostaglandins.3. The contractions produced by effluent collected from the third ventricle were due wholly or mainly to 5-HT, those from the inferior horn to the unknown hydroxy acid, and those from the anterior horn to both substances in varying proportions. In addition, some samples of effluent from the third ventricle seemed to contain catecholamines as well.4. The 5-HT in the effluent from the third ventricle is thought to be derived from the hypothalamus. The amounts assayed in 1 ml. effluent-the volume collected during 10 or 20 min perfusion-varied between 0.4 and 12 ng 5-HT. Output of 5-HT was initially high, then usually decreased but sometimes increased again during prolonged perfusion when temperature began to rise as anaesthesia lightened or when additional pentobarbitone sodium was given intravenously.5. When perfusion of the third ventricle was continued after death the 5-HT content in the effluent increased 3 to 24-fold during the first hour and then gradually declined. This post mortem rise in 5-HT output suggests an abnormal state of release of 5-HT from the hypothalamus. The theory is discussed that the same may happen in certain cases of brain injury and that the abnormal release of 5-HT would explain the pyrexia and shivering seen in such cases.6. The intraperitoneal injection of 5-hydroxytryptophan greatly increased the output of 5-HT in the effluent from the perfused third ventricle but only when this precursor of 5-HT was injected in large doses which caused respiratory arrest thus necessitating artificial ventilation. Upon the injection of 150 mg/kg the output of 5-HT rose to 90 ng/ml. and a further rise to 180 ng/ml. occurred when perfusion was continued after death.7. It was not possible to establish a relation between the presence of the hydroxy acid in the effluent from the inferior horn and neuronal activity.8. The 5-HT detected in the effluent from the anterior horn is assumed to have been released from the caudate nucleus.     

Effect on temperature of 5-hydroxytryptamine injected into the cerebral ventricles of cats

1. In unanaesthetized cats the effect on rectal temperature was examined of 5-HT injected through a Collison cannula chronically implanted into the left lateral ventricle. The response depended on the amount of 5-HT injected and on the solvent employed.2. An intraventricular injection of 200 mug 5-HT creatinine sulphate dissolved in 0.9% NaCl solution resulted in a long-lasting rise often interrupted initially by a transient fall in temperature.3. This fall became more prominent with larger doses of 5-HT; even more when the 5-HT was dissolved in distilled water, and then the hyperthermic effect was attenuated.4. It is concluded that intraventricular 5-HT raises rectal temperature in cats when the amount is not too large, and that a hypothermic effect when it occurs results from paralysis of cells in the anterior hypothalamus which are excited by small doses. This would be similar to the actions of acetylcholine in the perfused superior cervical ganglion of the cat, where small doses excite but large doses paralyse the ganglion cells.5. An intraventricular injection of distilled water produced a steady rise in temperature which is attributed to release of 5-HT.     

Temperature effects of reserpine injected into the cerebral ventricles of rabbits and cats

1. In unanaesthetized rabbits and cats reserpine was injected through a chronically implanted cannula in the left lateral cerebral ventricle, and rectal temperature was recorded.2. In rabbits the reserpine (0.5-0.6 mg) caused a rise in temperature, frequent defaecation and sedation. On repeating the intraventricular injections at 24 hr intervals the rise in temperature was not obtained with the second or third injection, but defaecation and sedation still occurred. When the hyperthermic response to intraventricular reserpine had disappeared the anterior hypothalamus still responded to intraventricular noradrenaline which produced a rise in temperature.3. In cats the reserpine (0.5-0.75 mg) caused a biphasic change in temperature, i.e. an initial fall followed by a rise, frequent defaecation, and catalepsy. On repeating the intraventricular injections at 24 hr intervals the initial hypothermic phase of the temperature response was not obtained with the second or third injection, but the late rise, defaecation and catalepsy were still produced. When the hypothermic phase had disappeared the hypothalamus still responded to intraventricular noradrenaline or adrenaline which produced a fall, and to intraventricular 5-hydroxytryptamine (5-HT) which produced a rise in temperature.4. It is concluded that the rise in temperature in rabbits and the initial fall produced in cats is not due to a direct action of reserpine on the cells of the anterior hypothalamus but to noradrenaline released from adrenergic fibres ending at these cells. When these fibres are depleted of their noradrenaline by one or two injections of reserpine, these effects are not obtained because noradrenaline is no longer available to be released in sufficient amounts to raise temperature in rabbits and to lower it in cats.     

The mechanism of body temperature changes induced by intraventricular injections of adrenaline, noradrenaline and 5-hydroxytryptamine in the ox (bos taurus)

1. Adrenaline, noradrenaline and 5-hydroxytryptamine (5-HT) were injected into the lateral ventricle of the ox. The effect of these drugs was measured on the respiratory rate, tidal volume, heat production, skin temperature of the ear, evaporative loss from the skin and the rectal temperature at 20 and 10 degrees C ambient temperature.2. Neither adrenaline (3 mg) nor noradrenaline (3 mg) had any effect on the temperature regulating mechanisms of the ox, except to produce vasoconstriction if vasodilatation was already present due to high ambient temperature or previous injection of 5-HT.3. Injection of 5-HT (5 mg) caused a rise in respiratory rate, a fall in tidal volume and heat production, elevation of ear skin temperature and skin evaporative loss and a decrease in rectal temperature. Sedation of the animals occurred.4. In its reaction to these monoamines the ox is similar to the goat, sheep and rabbit, but is unlike the cat and dog.5. It was concluded that neither adrenaline nor noradrenaline has a role in the central control of temperature regulation in the ox, but that 5-HT may be involved in the control of heat dissipation mechanisms.     

The effect of intraventricular injections of noradrenaline, 5-hydroxytryptamine, acetylcholine and tranylcypromine on the ox (Bos taurus) at different environmental temperatures

1. Noradrenaline, 5-hydroxytryptamine (5-HT), acetylcholine and tranylcypromine were injected or infused into the lateral ventricle of the ox. The effects of these drugs on heart and respiration rates, heat production, rectal, skin and hypothalamic temperatures and skin evaporative loss were measured when the animal was exposed to environmental temperatures ranging from -1 degrees C to +30 degrees C.2. Acetylcholine (0.001-2 mg) had no detectable effect on temperature regulation at 20 degrees C.3. In small doses (0.005-0.05 mg) 5-HT had no detectable effect. Larger doses (2-5 mg) given in a cold environment (-1 degrees C) also had no effect but the same doses given in warm environments (15-30 degrees C) caused increases in skin temperatures, skin evaporative loss and respiratory rate, and decreases in rectal and hypothalamic temperatures.4. Infusion of tranylcypromine (0.107 ml./min of a 1 in 50 solution) in a warm environment (20 degrees C) also caused a decrease in rectal temperature after a delay of 1-1(1/2) hr during which no effects were apparent.5. Noradrenaline (2 mg) had no effect on temperature regulation when injected into animals in a warm environment (30 degrees C). When injected (1 mg) into animals in a cold environment (-1 degrees C) shivering stopped and heat production and rectal and hypothalamic temperatures were decreased.6. It is concluded that intraventricular 5-HT and noradrenaline both cause a decrease in body temperature, and it is unlikely that central temperature regulation in the ox is mediated only by these two substances.     

A vasodepressor effect of pentobarbitone sodium

1. In anaesthetized cats under artificial ventilation, a few milligrams of pentobarbitone sodium injected into the cerebral ventricles produced a pronounced fall in arterial blood pressure, which was central in origin and resulted from inhibition of vasomotor tone.2. Pentobarbitone sodium was more effective in lowering blood pressure when injected into the cerebral ventricles than when injected into the cisterna magna, yet the pentobarbitone sodium did not act on structures in the ventricular wall, but acted on structures reached from the subarachnoid space.3. To produce its vasodepressor effect, the pentobarbitone sodium had to pass through the foramina of Luschka into the subarachmoid space beneath the medulla oblongata and to penetrate its ventral surface in a region caudal to the trapezoid bodies and lateral to the pyramids. This was the outcome of experiments in which the pentobarbitone sodium was injected into or perfused through the cerebral ventricles with or without an outflow cannula inserted into the aqueduct or into the fourth ventricle, and of experiments in which pentobarbitone sodium solutions were applied by means of Perspex rings to this region of the exposed ventral surface of the medulla. Whereas the application of pentobarbitone sodium to this region on one side had a weak vasodepressor effect only, its application on both sides produced a pronounced fall in arterial blood pressure.4. The region where pentobarbitone acted on topical application covers the region where nerve cells are found in the marginal glia immediately under the pia mater. The possibility is discussed that these cells are the morphological substrate on which the pentobarbitone acts, that arterial blood pressure is maintained by their activity which is suppressed by the pentobarbitone sodium.     

Further studies on prostaglandin E1 fever in cats

1. Micro-injections of a few nanograms of prostaglandin E(1) (PGE(1)) into the anterior hypothalamus of unanaesthetized cats produced a rise in rectal temperature, whereas temperature was not affected when micro-injections of even larger doses were made into the posterior hypothalamus. The hyperthermia produced by injections of PGE(1) into the cerebral ventricles is therefore attributed to an action of PGE(1) on the anterior hypothalamus.2. During a pentobarbitone sodium anaesthesia the sensitivity of cats to the hyperthermic effect of PGE(1) injected into the cerebral ventricles was found to be greatly reduced, particularly during the early stage of anaesthesia when body temperature was falling steeply.     

Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits

1. Prostaglandins were injected into the third ventricle of unanaesthetized cats and rabbits whilst rectal temperature was recorded.2. In cats prostaglandin E(1) and E(2) (PGE(1) and PGE(2)) produced hyperthermia which mostly began within a minute of injection and lasted 1 or more hours. With PGE(1) the hyperthermia was shown to be dose dependent between 10 ng and 10 mug (2.8 x 10(-11) and 2.8 x 10(-8)M). The hyperthermia was associated with vigorous shivering, skin vasoconstriction and piloerection. In several experiments a secondary rise in temperature occurred a few hours after the injection but such an effect was sometimes observed with control injections of 0.9% NaCl solution as well.3. None of the other prostaglandins (A(1), F(1alpha), F(2alpha)) examined in cats had an immediate or strong effect on temperature comparable to the hyperthermia produced by PGE(1) and PGE(2).4. In rabbits PGE(1) (2 mug) also caused hyperthermia which began shortly after the injection and lasted for hours. PGF(2alpha) and PGA(1), did not affect temperature.5. In cats it was seen that an intraperitoneal injection of 4-acetamidophenol (paracetamol 50 mg/kg) did not affect the initial strong hyperthermia produced by PGE(1) and PGE(2) but abolished the secondary rise.6. The possibility is discussed that PGE(1) plays a role as a central transmitter or modulator in temperature regulation.     

Changes in body temperature of the unanaesthetized monkey produced by sodium and calcium ions perfused through the cerebral ventricles

1. In the unanaesthetized Rhesus monkey, solutions containing sodium, calcium, potassium or magnesium in excess of the normal concentration of extracellular fluid were perfused from a lateral to the fourth ventricle through chronically implanted cannulae.2. Sodium (11.0-88.0 mM in excess of the physiological concentration) perfused through the ventricles, caused an immediate rise in body temperature which was accompanied by vasoconstriction, piloerection and shivering. The latency of the hyperthermia was related directly to the rate of perfusion and the concentration of sodium, whereas the magnitude of the response depended upon the concentration only. When the perfusion was terminated, shivering ceased and the temperature of the monkey returned to the base line level.3. When calcium ions were perfused in concentrations 2.5-47.9 mM in excess of that of extracellular fluid, a fall in the temperature of the animal occurred. The magnitude of the decreases depended upon the concentration of calcium in the perfusion fluid. Vasodilatation, sedation and a reduction in withdrawal reflexes accompanied the calcium-induced hypothermia. After the perfusion ended, the temperature continued to fall until the monkey began to shiver and vasoconstriction was observed in many skin areas.4. The perfusion through the cerebral ventricles with modified Krebs solution alone or with the Krebs solution which contained potassium or magnesium ions in concentrations five to ten times normal had virtually no effect on the temperature of the monkey.5. Since the temperature of the monkey was unchanged as long as the physiological ratio of sodium to calcium in the perfusion fluid remained constant, we conclude that the balance between these two essential cations within the brain stem could determine the neural mechanism whereby the set-point for body temperature of the primate is established.     

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

1. In the unanaesthetized rhesus monkey, 5-hydroxytryptamine (5-HT), catecholamines, acetylcholine or carbachol were micro-injected in a volume of 1.0 mul. or less through chronically implanted cannulae at eighty-six sites in the hypothalamus.2. 5-HT in doses of 2-10 mug caused a long-lasting elevation in temperature which was dose-dependent. An anatomical ;mapping' of the hypothalamus revealed that the hyperthermic action of 5-HT was localized to the anterior, pre-optic area directly ventral to the anterior commissure.3. Noradrenaline in doses of 1-12 mug produced a dose-dependent fall in temperature of short duration. An anatomical ;mapping' showed that the hypothermic action of this and other catecholamines was again localized to the anterior, pre-optic region.4. Acetylcholine, alone or in a mixture with eserine, or carbachol caused a dose-dependent hyperthermia which was characterized by an intense rise of short duration and vigorous shivering. A ;mapping' of this response revealed a diffuse patterning of sites throughout the hypothalamus which were sensitive to the application of acetylcholine and carbachol. However, in one circumscribed region at the junction between the posterior hypothalamus and mesencephalon, the two cholinomimetic substances caused a marked fall in temperature.5. We conclude that 5-HT activates a cholinergic heat production pathway which projects from the anterior to posterior hypothalamus. Noradrenaline, on the other hand, blocks the hyperthermic action of 5-HT rather than activates the heat loss system. A chemically mediated heat loss pathway apparently does not exist in the hypothalamus.     

Influence of the sympathetic nervous system on renal function during hypothermia

Hypothermia increases preglomerular vasoconstriction leading to decreases in renal blood flow (RBF) and glomerular filtration rate (GFR). Since plasma catecholamine concentrations are increased during hypothermia, the present study was performed to determine the role of the renal sympathetic nervous system in the cold-induced renal vasoconstriction. In Inactin® anaesthetized rats, hypothermia at 28 °C decreased GFR by 50% but failed to alter efferent renal sympathetic nerve activity (ERSNA). Since hypothermia causes shivering which could have influenced the ERSNA recording, Inactin® anaesthetized rats were treated with pethidine or rats were anaesthetized with pentobarbital sodium or Saffan® to eliminate cold-induced shivering. In these non-shivering rats, hypothermia produced a reversible decrease in ERSNA in association with a fall in GFR that was of a similar magnitude as in shivering rats. Further studies in Inactin® anaesthetized rats showed that the fall in GFR was unaltered by renal denervation, bilateral adrenalectomy or intrarenal administration of the α₁-adrenoceptor antagonist prazosin. We conclude that cold-induced renal vasoconstriction is not due to an increase in ERSNA or adrenaline/noradrenaline-mediated activation of renal α₁-adrenoceptors.     

The mechanism of the pyrogenic effect of streptococcus cell wall mucopeptide

1. The intravenous injection into rabbits of 25-50 mug of a preparation of cell-wall mucopeptide (SM) from group A streptococcus produced a rise in rectal temperature and a fall in the number of circulating granulocytes in the blood.2. The pyrogenic response to SM is not dependent on the circulating granulocytes since it occurred also in rabbits made leucopenic by nitrogen mustard (HN 3).3. The pyrogenic response to SM was enhanced after an intravenous injection of 5-hydroxytryptophan (5-HTP).4. Pre-treatment with reserpine caused a much greater attenuation of the pyrogenic response to SM than pre-treatment with alpha-methyl-para-tyrosine (AMPT).5. As the reserpine reduced the 5-hydroxytryptamine (5-HT) and noradrenaline level in the hypothalamus, whereas the AMPT reduced only the noradrenaline level, it is concluded that 5-HT may be involved in the pyrogenic response and the way in which 5-HT may exert this function is discussed.     

Continuous measurement of peripheral vascular resistance and circulatory function

Peripheral vascular resistance, stroke volume, cardiac output and maximum acceleration were computed in ‘real-time’ using aortic pressure and flow signals processed by simple analogue circuits incorporated into a multichannel recording system. The use of the system was exemplified by records of the haemodynamic effects of methoxamine and adrenaline in anaesthetized dogs and noradrenaline, isoprenaline and ephedrine in unanaesthetized dogs. These analogue techniques are applicable to circulatory studies in man.     

Electrical stimulation of the C1 region of the rostral ventrolateral medulla of the rat increases mean arterial pressure and adrenaline release in the posterior hypothalamus

By using intracerebral dialysis in combination with high performance liquid chromatography and electrochemical detection, extracellular posterior hypothalamic adrenaline, noradrenaline, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid were measured in the anaesthetized rat and changes in their levels monitored following administration of tranylcypromine and electrical stimulation of the rostral ventrolateral medulla. Tranylcypromine (10 mg/kg i.p.) administration decreased basal extracellular 3,4-dihydroxyphenylacetic acid and 5-hydroxyindole acetic acid levels with a simultaneous increase in adrenaline and noradrenaline levels. Electrical stimulation of the C1 area of the rostral ventrolateral medulla increased (+56.6%) extracellular adrenaline levels in the posterior hypothalamus with a simultaneous increase in mean arterial pressure (+48 mm Hg) compared to prestimulation control values. No change was seen in posterior hypothalamic extracellular levels of noradrenaline, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindole acetic acid during the stimulation period. Electrical stimulation of areas close to but outside the C1 region had no effect on either mean arterial pressure or posterior hypothalamic extracellular levels of the amines or the metabolites. The increase in adrenaline levels in the hypothalamus during stimulation of the C1 region supports the evidence for an adrenergic pathway from the rostral ventrolateral medulla to the hypothalamus and suggests that the increase in mean arterial pressure during electrical stimulation to the C1 region may relate to a specific increase in adrenaline levels.     

The influence of centrally applied noradrenaline on shivering and body temperature in the pigeon

1. Noradrenaline (NA) was injected in a volume of 1·0 μl. through chronically implanted cannula into the hypothalamus of the unanaesthetized pigeon.

2. In doses of 1-15 μg NA caused complete inhibition of shivering of dose-dependent duration. Histological mapping of the brain showed that NA was exerting its inhibitor action in the region above the optic chiasma bordering on the posterior hypothalamus and the anterior preoptic nucleus.

3. At low ambient temperature, the NA induced inhibition of the cold tremor caused a fall of core temperature which lasted as long as shivering was inhibited. Shivering induced by local cooling of the spinal cord, and by the combined cooling of the skin and the spinal cord, was likewise inhibited by the cerebral application of NA. There was no evidence of an adjustment of the temperature set-point by NA.

4. A rapid rise in skin temperature of the unfeathered feet, whenever NA was injected indicated a reduction in peripheral vasomotor tone.

     

The effect of noradrenaline and 5-hydroxytryptamine injected into a lateral cerebral ventricle, on thermoregulation in the new-born lamb.

1. Respiratory frequency, shivering, ear skin temperatures and rectal temperatures were observed following intraventricular injections of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and saline (NaCl) into new-born lambs exposed to ambient temperatures of 4, 21, or 30 degrees C. 2. Intraventricular NA caused respiratory rate to decrease and body temperature to increase in the 30 degrees C environment. At 21 degrees C, it increased ear skin temperature but did not significantly affect rectal temperature. At 4 degrees C, NA decreased shivering and rectal temperature fell. 3. 5-HT elevated respiratory rate in the 30 degrees C environment and increased ear skin temperature in the 21 and 4 degrees C environments. In the 4 degrees C environment rectal temperature decreased. 4. In general, the change in rectal temperature was related to the dosage of drug administered. Control injections of NaCl had no significant effect on any of the variables measured. 5. The monoaminergic pathways involved in thermoregulation in the new-born lamb appear to be organized in a manner similar to that of the adult sheep and are functional at birth.