We have examined the roles of three circumventricular organs, the area postrema, the subfornical organ, and the organum vasculosum of the lamina terminalis (OVLT), as possible access points for circulating pyrogens to cause fever. In conscious, unrestrained rats prepared with telemetry devices, intracerebroventricular cannulas, and intravenous catheters, body temperature was monitored after intravenously administered lipopolysaccharide and, on a different occasion, after intracerebroventricular prostaglandin E1. Lipopolysaccharide-induced fevers in sham control lesioned rats were indistinguishable from those observed in animals with lesions of the area postrema, the OVLT, or the tissue immediately adjacent to this structure (peri-OVLT). In contrast, rats with lesions of the subfornical organ displayed reduced fevers. In none of the groups of lesioned animals were prostaglandin E1 fevers reduced. Thus lesions did not interfere with central thermogenic pathways responsive to prostaglandin. Our results indicate that subfornical organ neurons respond to circulating pyrogens and through their efferent projections activate central pathways involved in fever.

Extracellular single unit recordings were obtained to investigate the effects of systemic administration of angiotensin II (ANG II) on the excitability of antidromically identified neurohypophysial neurons in the rat. Records were obtained from 89 oxytocin- or vasopressin-secreting neurons in the hypothalamic supraoptic or paraventricular nuclei. Increased excitability in response to ANG II was observed in 83% of putative vasopressin- and 75% of putative oxytocin-secreting neurons tested in intact animals. Lesion studies to identify the central nervous system site of action for such peripherally administered ANG II showed that, after electrolytic lesion of the rostral subfornical organ (SFO), neurohypophysial neurons demonstrated no increase in excitability in response to this peptide. In an attempt to correlate the synaptic events through which activation of SFO neurons may result in facilitated excitability of neurohypophysial cells, 19 cells were tested with both systemic ANG II and electrical stimulation in the SFO. These studies demonstrated that all cells which showed long-duration increases in excitability in response to electrical stimulation of SFO were also activated by systemic ANG II. It is concluded that the SFO is an essential central nervous system structure in eliciting increases in the excitability of both oxytocin- and vasopressin-secreting neurons in response to systemic ANG II. These effects may involve the activation of SFO efferents that evoke long-duration post-synaptic changes in neurohypophysial cell excitability.

SUMMARY1. Pregnant New Zealand white rabbits were kept from 14 days pre-partum at an environmental temperature of 33 TC, and their offspring were reared at this temperature.2. In response to a 4 hr cold exposure, animals (aged 90-180 days) raised in this way showed significant drops in colonic temperature (-27 + 05 TC) while control animals reared at 20 0C did not (+ 0 05 + 0 1 "C).3. A reduced, monophasic endotoxin fever was observed in animals reared at 33 "C, while a normal biphasic fever was seen in rabbits originally reared at 20 "0 and subsequently acclimated to 33 0C. 4. A greatly reduced temperature response to intravenous infusion ofnoradrenaline was also found in animals raised at 33 0C.5. It is proposed that thermal afferent input during early life may play an important role in the development of the thermoregulatory system.

We have identified, in urethan-anesthetized male Sprague-Dawley rats, a polysynaptic pathway connecting the subfornical organ (SFO) with the paraventricular nucleus (PVN) with a relay neuron in the medial septum-diagonal band of Broca (MS-DBB). Extracellular recordings were obtained from 136 MS-DBB neurons antidromically identified as projecting to the PVN. SFO stimulation orthodromically activated 79% of these cells (mean latency, 21.2 +/- 0.6 ms; mean duration, 6.0 +/- 0.2 ms), whereas stimulation in the fornix or hippocampal commissure had no effect. Of 35 identified MS-DBB neurons tested with systemic angiotensin II (ANG II), eight showed increases and six decreases in excitability that coincided with the ANG II-induced increase in blood pressure. To determine whether such changes were blood pressure related, 23 of the 35 identified MS-DBB neurons tested with ANG II were tested with systemic epinephrine. In every case the effect of epinephrine was similar to that of ANG II. These findings suggest that neurons in the MS-DBB receive afferent information from the SFO and the cardiovascular system. These cells in turn may activate neurons involved in the control of a variety of autonomic functions.

Sprague-Dawley rats were raised in an environmentally controlled room at 33 degrees C. Thermoregulatory responses of animals reared in this way were compared with those of control and warm-acclimated rats. Warm-reared animals demonstrated a significantly greater fall in colonic temperature during cold exposure when compared with both warm-acclimated (p less than 0.01) and control (p less than 0.001) animals. Warm-reared animals also show a modified response to central infusion of noradrenaline; they produce a hyperthermia in contrast with the hypothermia observed in control and warm-acclimated rats. These results suggest that the early thermal environment may modify the development of temperature regulation in the Sprague-Dawley rat in a way different from the normal acclimation process.