Conscious virgin, pregnant, or lactating rats were given intravenous Escherichia coli endotoxin while their temperatures were monitored telemetrically. Virgin females responded to 10-50 micrograms/kg endotoxin with a slight hypothermia, followed by a fever of nearly 2 degrees C magnitude. In pregnant rats given 25 micrograms/kg of the endotoxin, fevers were reduced between 96 h before and 24 h after parturition compared with those seen in virgins or in lactating rats > 24 h postpartum. In the 24-h period before expected time of parturition, no rat developed a fever and the majority of animals became hypothermic; furthermore, in 80% of such animals given 25 micrograms/kg endotoxin, the hypothermia was accompanied by death within 3-15 h. Some mortality and hypothermia were also seen up to 48 h before birth and up to 24 h after birth. No mortality was observed in virgin, pregnant, or lactating rats outside of this time period. We conclude that, around the time of delivery, there is a suppression of fever in the rat and occasional toxic responses to endotoxin.

SUMMARY1. The antipyretic effect of arginine vasopressin (AVP) introduced into the brain by push-pull perfusion was investigated in the sheep.2. Control perfusions with sucrose solutions had no effect on fevers induced by a bacterial endotoxin. Sucrose solutions containing AVP (4.0,g/ml.) perfused at 40 ,dl./min had significant antipyretic activity, reducing the two peaks of the fever but had no effect on resting body temperature.3. Loci in which AVP induced antipyresis were limited to the septal region about 2-3 mm anterior to the anterior commissure.4. The amounts of AVP in perfusates from the septal region correlated negatively with changes in body temperature.5. AVP administered i.v. did not lower fever. 6. AVP plasma levels correlated negatively with fever magnitude following premature birth induced by dexamethasone.

The nucleus tractus solitarius/dorsal motor nucleus of the vagus nerve (NTS/DMV) area was perfused by the push-pull perfusion technique in anesthetized rats, and perfusates were assayed for arginine vasopressin (AVP) and oxytocin (OXT) immunoreactivity. As compared with controls, electrical stimulation of the ipsilateral paraventricular nucleus (PVN) resulted in increased amounts of both AVP (approximately 5-fold) and OXT (approximately 10-fold, P less than 0.05 each) in the perfusates. During the poststimulation perfusion period, peptide concentrations were found to return to control levels. Elevation of circulating AVP and OXT by an osmotic stimulus did not result in increases of AVP and OXT in NTS/DMV perfusates. These data suggest that AVP and OXT are released from NTS/DMV area fiber terminals during electrical stimulation of descending PVN neurons. Furthermore, they are consistent with the view that both peptides are involved as neurotransmitters in autonomic regulation.

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Arginine vasopressin (AVP) was administered into the lateral cerebral ventricles of rats to assess its effects when given directly into the brain. AVP (1.0 microgram) caused an immediate sharp decrease in body temperature. Behaviorally, AVP caused short pauses of immobility and staring upon the first injection but the same dose caused myoclonic-myotonic convulsions upon the second injection 2 days later. Thereafter, as little as 10 ng of AVP caused seizures.

SUMMARY1. A method is described for the perfusion of the liquor space from a lateral cerebral ventricle to the cisterna magna in the unanaesthetized cat.Perfusions were carried out for 30-40 min using various physiological salt solutions whilst rectal temperature was recorded.2. When the salt solution used contained calcium in the physiological concentration, rectal temperature remained unchanged, but when it contained no calcium an intense hyperthermia developed during the perfusion. The finding that calcium must be present in the perfusion fluid for preventing temperature from rising may lead to a new understanding of the working of the 'set-point' in the control of body temperature and of the mechanism of action of pyrogens.3. Independent of the nature of the perfusion fluid a long-lasting late rise in temperature developed after a perfusion. This happened regularly when the infusion needle was inserted only into the hub of the ventricular cannula, but rarely when the needle was extended beyond the tip of the cannula shaft and the cannula had been flushed out during the preceding days. It is therefore thought that an unknown pyrogenic factor present in the lumen of the cannula and washed into the ventricle with the perfusion fluid is responsible for this effect.4. The effluent collected from the cisterna contracted the fundus strip of the rat stomach. As the contractions were little affected by BOL, they are attributed mainly to an action of prostaglandin E1 and not to an action of 5-HT.

Preference for ethyl alcohol was significantly reduced or totally abolished in rats given orally p-chlorophenylalanine, a tryptophan hydroxylase inhibitor that selectively depletes brain serotonin. Some aversion to alcohol was observed while p-chlorophenylalanine was administered, but the rats' rejection of alcohol was even more marked after the drug was discontinued. Oral administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor that depletes brain catecholamines, slightly reduced selection of alcohol, but preference returned to normal as soon as alpha-methyl-p-tyrosine was terminated.

Urethan-anesthetized rats were used to identify effective stimuli for the release of the peptides arginine vasopressin (AVP) and oxytocin into the ventral septal area (VSA) of the brain. Febrile responses to intracerebroventricular injection of prostaglandin E1 (PGE1) were observed in rats whose body temperatures were maintained at 35, 37, or 39 degrees C. Microinjection of the AVP antagonist d(CH2)5Tyr(Me)AVP into the VSA enhanced fever only when PGE1 administration was associated with a significant rise in body temperature. Passive elevation ("artificial fever") or reduction of body temperature in the absence of a PGE1 stimulus was not affected by the antagonist. Push-pull perfusion of the VSA and the dorsal hippocampus, followed by radioimmunoassay of perfusates for AVP and oxytocin, revealed enhanced release into the VSA of AVP only when PGE1 administration was followed by a rise in body temperature. Oxytocin was released whenever body temperature was raised. Peptide concentrations in simultaneous perfusates of dorsal hippocampus did not change in response to PGE1 administration or to passive elevation of body temperature. We conclude that AVP is released into the VSA, but not the dorsal hippocampus, of the rat during a fever induced by PGE1. Oxytocin is released into the VSA, but not the hippocampus, when temperature is elevated.