Is prostaglandin fever mediated by the presynaptic release of hypothalamic 5-HT or norepinephrine?

An array of guide tubes to accommodate concentric push-pull cannulae was implanted chronically within the diencephalon of the rhesus or other species of macaque monkey which was accustomed to a primate chair. Colonic and skin temperatures were monitored continuously during each experiment in which a circumscribed site in the monkey's hypothalamus had been labelled by microinjection of 50-100 muCi serotonin (3H-5-HT) or 50-100 muCi or norepinephrine (3H-NE). Consecutive push-pull perfusions with an artificial CSF were carried out for 10 min at a rate of 50 mul/min at 20 min intervals. Under the control condition, a declining washout curve of radioactivity was obtained over 8-10 perfusions. Prostaglandin (PG) E1 in a concentration of 10-20 ng/min was added to the artificial CSF during the third and fifth successive perfusions. Nonlabelled PGE1 failed to exert a precise and consistent effect on the characteristic pattern of efflux of either tritiated 5-HT or NE from perfusion sites distributed widely throughout the hypothalamus and adjacent structures. However, in some experiments, an enhanced efflux of the indoleamine label did occur after the temperature had begun to rise following a perfusion with the PGE. In still other experiments, 15-20 muCi 3H-PGE1 was microinjected to label a perfusion site. Again the addition of either nonlabelled 5-HT or NE to the perfusion fluid produced an unreliable change or no alteration in the efflux of 3H-ge1 from sites in the anterior as well as other parts of the hypothalamus. These findings indicate that prostaglandin injected into the brain does not evoke hyperthemia by way of a pathological disturbance to the balance in the presynaptic release of 5-HT and NE within nerve endings in the rostral hypothalamus of the monkey. Conversely, neither 5-HT nor NE influences the prostaglandin activity within the hypothalamus, at least in so far as a functional change in the body temperature of the primate is concerned.