SUAMMVARY1. Prostaglandins were injected into the third ventricle of unanaesthetized cats and rabbits whilst rectal temperature was recorded.2. In cats prostaglandin E1 and E2 (PGE1 and PGE2) produced hyperthermia which mostly began within a minute of injection and lasted 1 or more hours. With PGE1 the hyperthermia was shown to be dose dependent between 10 ng and 10 ,tg (2.8 x 10-11 and 2.8 x 10-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 (A1, F1,, F2X) examined in cats had an immediate or strong effect on temperature comparable to the hyperthermia produced by PGE1 and PGE2.4. In rabbits PGE1 (2 fg) also caused hyperthermia which began shortly after the injection and lasted for hours. PGF2a and PGA1, 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 PGE1 and PGE2 but abolished the secondary rise.6. The possibility is discussed that PGE1 plays a role as a central transmitter or modulator in temperature regulation.

1. Samples of cisternal cerebrospinal fluid (c.s.f.) were collected from unanaesthetized cats while rectal temperature was continuously recorded. From the same cat, samples were collected during normal body temperature, during pyrogen fever and when the fever was brought down by an I.P. injection of an antipyretic. Fever was produced by injection of the bacterial pyrogen of Shigella dysenteriae either into the third ventricle, cisterna magna or I.V. The samples of c.s.f. were assayed for PGE1‐like activity on the rat stomach fundus strip preparation rendered insensitive to 5‐HT. 2. In samples of c.s.f. collected during normal body temperature, usually either no PGE1‐like activity was detected, or its activity was low. Higher values were obtained in only a few cats. 3. In each experiment the PGE1‐like activity increased, often many‐fold, in samples collected during the pyrogen fever, irrespective, of the route of administration of the pyrogen. However, on I.V. injection, about 1000 times larger doses of the pyrogen were required than on injection into the liquor space to produce fever and the increase in PGE1‐like activity of cisternal c.s.f. 4. The antipyretic drugs indomethacin, paracetamol and aspirin, injected I.P. during the pyrogen fever, brought down temperature, and the PGE1‐like activity of the cisternal c.s.f. again became low. 5. When samples of cisternal c.s.f. were subjected to thin layer chromatography the prostaglandin‐like activity was solely or mainly found in the zone corresponding to the prostaglandins of the E series. 6. These findings support the theory that pyrogens produce fever by increasing synthesis and release of prostaglandin in the preoptic anterior hypothalamic area, and that antipyretics of the aspirin type bring down this fever because they inhibit this synthesis. 7. It is concluded that pyrogen increases prostaglandin synthesis not only in the preoptic anterior hypothalamic area. When injected into the liquor space increased synthesis of prostaglandin probably occurs in many regions near the surface of the brain stem, and when injected I.V. may occur in other parts of the C.N.S. as well. But to produce fever the prostaglandin has to act on the preoptic anterior hypothalamic area.

SUMMARY1. Experiments were carried out in unanaesthetized cats to find out if a prostaglandin is the mediator (a) for the long lasting fever which often follows injections of phsyiological salt solutions into the cerebral ventricles or into the cisterna magna, as well as their perfusions through the cerebral ventricles, and (b) for the sodium fever which occurs during a perfuslion of the cerebral ventricles with calcium-free artificial c.s.f. A fever mediated by prostaglandin should be accompanied by an increase of prostaglandin activity in cisternal c.s.f., and be abolished or prevented by antipyretics like paracetamol or indomethacin which inhibit prostaglandin synthesis. Both criteria were applied.2. The fever which follows injections or perfusions of physiological salt solutions appears to be mediated by a prostaglandin of the E series, probably E2 (PGE2) because it was accompanied by increased prostaglandin E-like activity in the c.s.f. and abolished by paracetamol and indomethacin. During the first few days after pre-treatment of the cats with intramuscular chloramphenicol the injections were rarely followed by fever.3. The fever which occurs during a perfusion with calcium-free artificial c.s.f. appears not to be mediated by prostaglandin, because it was not associated with increased prostaglandin activity in the cisternal effluent, and not prevented by paracetamol or indomethacin, although these antipyretics usually attenuated the fever.4. A perfusion of the cerebral ventricles with artificial c.s.f. containing calcium in an abnormally high concentration (6. 25 mm) brought down fever produced by PGE1, or PGE2, or bacterial pyrogen.

Corticosterone (3–12 mg kg−1, i.p., giving rise to plasma corticosterone concentrations from 26.7 to 89.0 μg/100 ml) failed to have a significant anxiogenic action. Instead, corticosterone (3 mg kg−1) had a significant anxiolytic effect in the social interaction test of anxiety. Adrenalectomized rats had very low levels of social interaction; but adrenalectomized rats that had been given replacement corticosterone therapy did not differ from the shamoperated controls. Thus, corticosterone appears to have the opposite effect to that previously reported for ACTH. Possible mechanisms for the observed results are discussed.

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