A subsidiary fever center in the medullary raphé?

In fever, as in normal thermoregulation, signals from the preoptic area drive both cutaneous vasoconstriction and thermogenesis by brown adipose tissue (BAT). Both of these responses are mediated by sympathetic nerves whose premotor neurons are located in the medullary raphé. EP3 receptors, key prostaglandin E2 (PGE2) receptors responsible for fever induction, are expressed in this same medullary raphé region. To investigate whether PGE2 in the medullary raphé might contribute to the febrile response, we tested whether direct injections of PGE2 into the medullary raphé could drive sympathetic nerve activity (SNA) to BAT and cutaneous (tail) vessels in anesthetized rats. Microinjections of glutamate (50 mM, 60-180 nl) into the medullary raphé activated both tail and BAT SNA, as did cooling the trunk skin. PGE2 injections (150-500 ng in 300-1,000 nl) into the medullary raphé had no effect on tail SNA, BAT SNA, body temperature, or heart rate. By contrast, 150 ng PGE2 injected into the preoptic area caused large increases in both tail and BAT SNA (+60 +/- 17 spikes/15 s and 1,591 +/- 150% of control, respectively), increased body temperature (+1.8 +/- 0.2 degrees C), blood pressure (+17 +/- 2 mmHg), and heart rate (+124 +/- 19 beats/min). These results suggest that despite expression of EP3 receptors, neurons in the medullary raphé are unable to drive febrile responses of tail and BAT SNA independently of the preoptic area. Rather, they appear merely to transmit signals for heat production and heat conservation originating from the preoptic area.     

Central circuitries for body temperature regulation and fever

Body temperature regulation is a fundamental homeostatic function that is governed by the central nervous system in homeothermic animals, including humans. The central thermoregulatory system also functions for host defense from invading pathogens by elevating body core temperature, a response known as fever. Thermoregulation and fever involve a variety of involuntary effector responses, and this review summarizes the current understandings of the central circuitry mechanisms that underlie nonshivering thermogenesis in brown adipose tissue, shivering thermogenesis in skeletal muscles, thermoregulatory cardiac regulation, heat-loss regulation through cutaneous vasomotion, and ACTH release. To defend thermal homeostasis from environmental thermal challenges, feedforward thermosensory information on environmental temperature sensed by skin thermoreceptors ascends through the spinal cord and lateral parabrachial nucleus to the preoptic area (POA). The POA also receives feedback signals from local thermosensitive neurons, as well as pyrogenic signals of prostaglandin E(2) produced in response to infection. These afferent signals are integrated and affect the activity of GABAergic inhibitory projection neurons descending from the POA to the dorsomedial hypothalamus (DMH) or to the rostral medullary raphe region (rMR). Attenuation of the descending inhibition by cooling or pyrogenic signals leads to disinhibition of thermogenic neurons in the DMH and sympathetic and somatic premotor neurons in the rMR, which then drive spinal motor output mechanisms to elicit thermogenesis, tachycardia, and cutaneous vasoconstriction. Warming signals enhance the descending inhibition from the POA to inhibit the motor outputs, resulting in cutaneous vasodilation and inhibited thermogenesis. This central thermoregulatory mechanism also functions for metabolic regulation and stress-induced hyperthermia.     

Abnormal brain activation to visual stimulation in cocaine abusers

Chronic cocaine abuse has been associated with cerebrovascular pathology. This is likely to reflect its vasoactive effects; cocaine produces vasoconstriction and reduces cerebral blood flow. We propose that cerebrovascular pathology in chronic cocaine abusers would result in abnormal BOLD [blood oxygenation level dependent] responses to activation stimuli. Here, we used fMRI to compared the BOLD response to photic visual stimulation in neurologically intact active cocaine abusers to that in non-drug-using healthy controls. Cocaine abusers showed a significantly enhanced positive BOLD response to photic stimulation when compared to control subjects. The enhanced activation in the cocaine abusers could result from low resting cerebral blood flow secondary to increased vasoconstriction and/or from low oxidative metabolism during activation. Alternatively, the larger signal intensity in the cocaine abusers could result from inefficient neuronal processing as has been shown to occur in other conditions of cerebral pathology. These findings provide evidence of cerebral dysfunction with chronic cocaine abuse, which could reflect cerebral blood flow or neuronal changes. Further studies are required to determine if the cerebrovascular changes we observed in the cocaine abusers recover with detoxification and to assess their functional consequences.     

Activation of slowly conducting medullary raphe-spinal neurons, including serotonergic neurons, increases cutaneous sympathetic vasomotor discharge in rabbit

Neurons in the rostral medullary raphe/parapyramidal region regulate cutaneous sympathetic nerve discharge. Using focal electrical stimulation at different dorsoventral raphe/parapyramidal sites in anesthetized rabbits, we have now demonstrated that increases in ear pinna cutaneous sympathetic nerve discharge can be elicited only from sites within 1 mm of the ventral surface of the medulla. By comparing the latency to sympathetic discharge following stimulation at the ventral raphe site with the corresponding latency following stimulation of the spinal cord [third thoracic (T3) dorsolateral funiculus] we determined that the axonal conduction velocity of raphe-spinal neurons exciting ear pinna sympathetic vasomotor nerves is 0.8 +/- 0.1 m/s (n = 6, range 0.6-1.1 m/s). Applications of the 5-hydroxytryptamine (HT)(2A) antagonist trans-4-((3Z)3-[(2-dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl)propen-1-yl)-phenol, hemifumarate (SR-46349B, 80 microg/kg in 0.8 ml) to the cerebrospinal fluid above thoracic spinal cord (T1-T7), but not the lumbar spinal cord (L2-L4), reduced raphe-evoked increases in ear pinna sympathetic vasomotor discharge from 43 +/- 9 to 16 +/- 6% (P < 0.01, n = 8). Subsequent application of the excitatory amino acid (EAA) antagonist kynurenic acid (25 micromol in 0.5 ml) substantially reduced the remaining evoked discharge (22 +/- 8 to 6 +/- 6%, P < 0.05, n = 5). Our conduction velocity data demonstrate that only slowly conducting raphe-spinal axons, in the unmyelinated range, contribute to sympathetic cutaneous vasomotor discharge evoked by electrical stimulation of the medullary raphe/parapyramidal region. Our pharmacological data provide evidence that raphe-spinal neurons using 5-HT as a neurotransmitter contribute to excitation of sympathetic preganglionic neurons regulating cutaneous vasomotor discharge. Raphe-spinal neurons using an EAA, perhaps glutamate, make a substantial contribution to the ear sympathetic nerve discharge evoked by raphe stimulation.     

Effects of invariant sympathetic activity on cutaneous circulatory responses to heat stress

This study investigated the role of sympathetic withdrawal on blood flow responses in cutaneous arteriovenous anastomoses (AVAs) and capillaries to direct and indirect heat stress. This was achieved by clamping sympathetic activity (SC) to the tail of anesthetized rats so that constrictor tone remained invariant during exposure of either the animal's tail (direct heating) or body (indirect heating) to a 35 degrees C environment. Flow through the AVAs in the tail was evaluated by laser-Doppler flowmetry (LDF), while capillary flow was investigated by videodensitometry measurements of blood cell velocity (CBV) in single capillaries within the subepidermal vascular plexus. Both direct and indirect heating significantly increased LDF and CBV. In comparison to blood flow responses in sham-operated control rats, the SC procedure resulted in significantly lower LDF responses to both direct and indirect heat stress. By contrast, the response of CBV was not significantly affected by SC during either mode of heating. These results indicate that the withdrawal of sympathetic constrictor tone plays a role in the response of cutaneous AVAs, but not precapillary arterioles, to direct as well as indirect heat stress. Additional studies on unanesthetized animals showed that superimposing body heating on a base of local heating elicited a further increase in LDF, suggesting that local heating does not deplete neural mediated dilatory reserve.     

Patterns of constriction produced by vasoactive agents

The patterns of vasoconstriction produced by local infusions of constrictor agents and neurogenic stimuli are unique and varied. Although vasoconstrictors or neurogenic stimuli may produce similar increases in total resistance to blood flow, the effects on consecutive vascular segments may differ dramatically. Vasoconstrictors may affect primarily small vessels, large vessels, or a combination of both. The constrictor response may be restricted to precapillary vessels or may recruit both pre- and postcapillary vessels. The baroreceptors elicit a pattern of vasoconstriction distinct from that produced by electrical stimulation of a vasomotor nerve. Prearteriolar and venous resistance may contribute more than arterioles to increases in total vascular resistance produced by local infusions of vasoconstrictor agents or nerve stimulation. The constriction of large vessels also affects fluid filtration, vascular capacity, and the distribution of blood flow between shunt and exchange vessels. The waning of the resistance increase that occurs during prolonged infusions of vasoconstrictors varies, in part, as a function of the vessel segments that participate in the vasoconstrictor response. Large vessels participate in vasoconstrictor responses triggered by stimuli that impose a severe stress on the circulation. In contrast, small vessels participate primarily in normal vascular adjustments required to maintain blood pressure at the set point.     

Medullary raphe neuron activity is altered during fictive cough in the decerebrate cat.

Chemical lesions in the medullary raphe nuclei region influence cough. This study examined whether firing patterns of caudal medullary midline neurons were altered during cough. Extracellular neuron activity was recorded with microelectrode arrays in decerebrated, neuromuscular-blocked, ventilated cats. Cough-like motor patterns (fictive cough) in phrenic and lumbar nerves were elicited by mechanical stimulation of the intrathoracic trachea. Discharge patterns of respiratory and nonrespiratory-modulated neurons were altered during cough cycles (58/133); 45 increased and 13 decreased activity. Fourteen cells changed firing rate during the inspiratory and/or expiratory phases of cough. Altered patterns in 43 cells were associated with the duration of, or extended beyond, the cough episodes. The different response categories suggest that multiple factors influence the discharge patterns during coughing: e.g., respiratory-modulated and tonic inputs and intrinsic connections. These results suggest involvement of midline neurons (i.e., raphe nuclei) in the cough reflex.     

The dorsomedial hypothalamus: a new player in thermoregulation

Neurons in the dorsomedial hypothalamus (DMH) play key roles in physiological responses to exteroceptive ("emotional") stress in rats, including tachycardia. Tachycardia evoked from the DMH or seen in experimental stress in rats is blocked by microinjection of the GABA(A) receptor agonist muscimol into the rostral raphe pallidus (rRP), an important thermoregulatory site in the brain stem, where disinhibition elicits sympathetically mediated activation of brown adipose tissue (BAT) and cutaneous vasoconstriction in the tail. Disinhibition of neurons in the DMH also elevates core temperature in conscious rats and sympathetic activity to least significant difference interscapular BAT (IBAT) and IBAT temperature in anesthetized preparations. The latter effects are blocked by microinjection of muscimol into the rRP, while microinjection of muscimol into either the rRP or DMH suppresses increases in sympathetic nerve activity to IBAT, IBAT temperature, and core body temperature elicited either by microinjection of PGE(2) into the preoptic area (an experimental model for fever), or central administration of fentanyl. Neurons concentrated in the dorsal region of the DMH project directly to the rRP, a location corresponding to that of neurons trans-synaptically labeled from IBAT. Thus these neurons control nonshivering thermogenesis in rats, and their activation signals its recruitment in diverse experimental paradigms. Evidence also points to a role for neurons in the DMH in thermoregulatory cutaneous vasoconstriction, shivering, and endocrine adjustments. These directions provide intriguing avenues for future exploration that may expand our understanding of the DMH as an important hypothalamic site for the integration of autonomic, endocrine, and behavioral responses to diverse challenges.     

电刺激猫中脑导水管周围灰质和中缝大核对脊髓背角神经元伤害性感受反应的抑制

1.在氯醛糖麻醉的猫上,观察了电刺激中脑导水管周围灰质(PAG)和中缝大核(NRM)对脊髓腰段背角神经元传入活动的影响。2.按照对刺激的反应型式,在背角记录到非伤害性低阈值传入、广动力范围、伤害性热敏以及高阈值传入诱发的自发放电抑制等四类神经元。3.刺激 PAG和 NRM对记录到的多数背角神经元皮肤传入反应有明显抑制效应,而对自发放电抑制性神经元产生去抑制。4.比较刺激两脑区的抑制效应:NRM 作用较PAG 强;PAG 活动对背角伤害性反应抑制的选择性较 NRM强;阿片肽拮抗剂-纳洛酮拮抗NRM刺激的抑制。5.这些结果提示PAG和NRM对脊髓的下行抑制,可能有一部分是通过不同神经机制实现的。     

Role of NO and COX pathways in mediation of adenosine A1 receptor-induced renal vasoconstriction

The mechanism of adenosine A1 receptor-induced intrarenal vasoconstriction is unclear; it depends on sodium intake and may be mediated by changing the intrarenal activity of the nitric oxide (NO) and/or cyclooxygenase (COX) pathway of arachidonic acid metabolism. The effects of 2-chloro-N(6)-cyclopentyl-adenosine (CCPA), a selective A1 receptor agonist, on renal hemodynamics were examined in anesthetized rats maintained on high sodium (HS) or low sodium (LS) diet. Total renal (i.e., cortical) blood flow (RBF) as well as superficial cortical (CBF), outer medullary (OMBF), and inner medullary (IMBF) flows were determined by laser-Doppler. In HS rats, suprarenal aortic infusions of 8-40 nmol/kg/hr CCPA decreased IMBF (15%) and other perfusion indices (22%-27%); in LS rats, IMBF increased 3% (insignificant) and other indices decreased 13%-24%. In LS rats, pretreatment with N-nitro-L-arginine methyl ester prevented the A1 receptor-mediated decrease in RBF and CBF but not OMBF; the response in IMBF was not altered. Pretreatment with indomethacin prevented the decreases in RBF, CBF, and OMBF and did not change the response of IMBF. Thus, within the cortex the vasoconstriction that follows A1 receptor activation results both from inhibition of NO synthesis and from stimulation of vasoconstrictor products of the COX pathway. In the outer medulla, the latter products seem exclusively responsible for CCPA-induced vasoconstriction. The observation that in LS rats IMBF was not affected by stimulation of adenosine A1 receptors suggests that limiting salt intake may help protect medullary perfusion against vasoconstrictor stimuli which have the potential to disturb long-term control of arterial pressure.     

Differential Effects of Ipsapirone on 5-Hydroxytryptamine Release in the Dorsal and Median Raphe Neuronal Pathways

Abstract: Serotonergic neurons of the dorsal and median raphe nuclei are morphologically dissimilar. Recent results challenge previous evidence indicating a greater inhibition of dorsal raphe neurons after 5-hydroxytryptamine_1A (5-HT_1A) autoreceptor activation. As both nuclei innervate different forebrain territories, this issue is critical to understanding the changes in brain function induced by anxiolytic and antidepressant drugs. Using microdialysis, we examined the modifications of 5-HT release induced by the selective 5-HT_1A agonist ipsapirone in both neuronal pathways. Maximal and minimal basal 5-HT values (in the presence of 1 µ M citalopram) were 45.0 ± 4.8 fmol/fraction in the median raphe nucleus and 8.4 ± 0.4 fmol/fraction in the dorsal hippocampus. Ipsapirone (0.3, 3, and 10 mg/kg s.c.) reduced dose-dependently 5-HT in the two raphe nuclei and four forebrain areas. Maximal reductions (to ∼25% of predrug values) were observed in cortex and striatum and in median raphe nucleus. The effects were more moderate in dorsal and ventral hippocampus (to 66 and 50% of baseline, respectively). These results are consistent with a higher sensitivity of dorsal raphe neurons to 5-HT_1A autoreceptor activation. Yet the differential reduction of 5-HT release in the median raphe nucleus and hippocampus suggests the presence of complex mechanisms of control of 5-HT release in these neurons.     

Role of the hypothalamic PVN in the reflex reduction in mesenteric blood flow elicited by hyperthermia

The hypothalamic paraventricular nucleus (PVN) is an important integrative center in the brain. In the present study, we investigated whether the PVN is a key region in the mesenteric vasoconstriction that normally accompanies an increase in core body temperature. Anesthetized rats were monitored for blood pressure, heart rate, mesenteric blood flow, and vascular conductance. In control rats, elevation of core body temperature to 41 degrees C had no significant effect on blood pressure, increased heart rate, and reduced mesenteric blood flow by 21%. In a separate group of rats, muscimol was microinjected bilaterally (1 nmol/side) into the PVN. Compared with the control group, there was no significant difference in the blood pressure and heart rate responses elicited by the increase in core body temperature. In contrast to control animals, however, mesenteric blood flow did not fall in the muscimol-treated rats in response to the elevation in core body temperature. In a separate group, in which muscimol was microinjected into regions outside the PVN, elevating core body temperature elicited the normal reduction in mesenteric blood flow. The results suggest that the PVN may play a key role in the reflex decrease in mesenteric blood flow elicited by hyperthermia.     

Chronic fluoxetine microdialysis into the medullary raphe nuclei of the rat, but not systemic administration, increases the ventilatory response to CO2.

In conscious rats, focal CO2 stimulation of the medullary raphe increases ventilation, whereas interference with serotonergic function here decreases the ventilatory response to systemic hypercapnia. We sought to determine whether repeated administration of a selective serotonin reuptake inhibitor in this region would increase the ventilatory response to hypercapnia in unanesthetized rats. In rats instrumented with electroencephalogram-electromyogram electrodes, 250 or 500 microM fluoxetine or artificial cerebrospinal fluid (aCSF) was microdialyzed into the medullary raphe for 30 min daily over 15 days. To compare focal and systemic treatment, two additional groups of rats received 10 mg x kg(-1) x day(-1) fluoxetine or vehicle systemically. Ventilation was measured in normocapnia and in 7% CO2 before treatment (day 0), acutely (days 1 or 3), on day 7, and on day 15. There was no change in normocapnic ventilation in any treatment group. Rats that received 250 microM fluoxetine microdialysis showed a significant 13% increase in ventilation in wakefulness during hypercapnia on day 7, due to an increase in tidal volume. In rats microdialyzed with 500 microM fluoxetine, there were 16 and 32% increases in minute ventilation during hypercapnia in wakefulness and sleep on day 7, and 20 and 28% increases on day 15, respectively, again due to increased tidal volume. There was no change in the ventilatory response to CO2 in rats microdialyzed with aCSF or in systemically treated rats. Chronic fluoxetine treatment in the medullary raphe increases the ventilatory response to hypercapnia in an unanesthetized rat model, an effect that may be due to facilitation of chemosensitive serotonergic neurons.     

Cortical and subcortical localization of response to pain in man using positron emission tomography.

A quantitative study of the regional cerebral responses to non-painful and painful thermal stimuli in six normal volunteers has been done by monitoring serial measurements of regional blood flow measured by positron emission tomography (PET). In comparison to a baseline of warm stimulation no statistically significant changes in blood flow were seen in relation to increasing non-painful heat. However, highly significant increases in blood flow were seen in response to painful heat in comparison to non-painful heat. These changes were in the contralateral cingulate cortex, thalamus and lenticular nucleus. These findings are discussed in relation to previous physiological observations of responses to nociceptive stimuli in man and primates.     

中缝背核对猫小脑浦肯野细胞电活动的影响

在麻醉并麻痹的猫上观察到:刺激中缝背核(DR)可引起小脑皮层浦肯野细胞(PC)兴奋或抑制(主要是抑制);由被动性腕关节屈伸运动刺激引起的外周本体传入可以增强或减速PC对DR刺激的反应。这些结果表明中缝-小脑5-HT能纤维的传入活动可以调制PC的放电活动,并与外周传入有相互作用。     

Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor responses in humans.

This study tested the hypothesis that head-down tilt bed rest (HDBR) reduces adrenergic and nonadrenergic cutaneous vasoconstrictor responsiveness. Additionally, an exercise countermeasure group was included to identify whether exercise during bed rest might counteract any vasoconstrictor deficits that arose during HDBR. Twenty-two subjects underwent 14 days of strict 6 degrees HDBR. Eight of these 22 subjects did not exercise during HDBR, while 14 of these subjects exercised on a supine cycle ergometer for 90 min a day at 75% of pre-bed rest heart rate maximum. To assess alpha-adrenergic vasoconstrictor responsiveness, intradermal microdialysis was used to locally administer norepinephrine (NE), while forearm skin blood flow (SkBF; laser-Doppler flowmetry) was monitored over microdialysis membranes. Nonlinear regression modeling was used to identify the effective drug concentration that caused 50% of the cutaneous vasoconstrictor response (EC(50)) and minimum values from the SkBF-NE dose-response curves. In addition, the effects of HDBR on nonadrenergic cutaneous vasoconstriction were assessed via the venoarteriolar response of the forearm and leg. HDBR did not alter EC(50) or the magnitude of cutaneous vasoconstriction to exogenous NE administration regardless of whether the subjects exercised during HDBR. Moreover, HDBR did not alter the forearm venoarteriolar response in either the control or exercise groups during HDBR. However, HDBR significantly reduced the magnitude of cutaneous vasoconstriction due to the venoarteriolar response in the leg, and this response was similarly reduced in the exercise group. These data suggest that HDBR does not alter cutaneous vasoconstrictor responses to exogenous NE administration, whereas cutaneous vasoconstriction of the leg due to the venoarteriolar response is reduced after HDBR. It remains unclear whether attenuated venoarteriolar responses in the lower limbs contribute to reduced orthostatic tolerance after bed rest and spaceflight.     

Fever response to intravenous prostaglandin E2 is mediated by the brain but does not require afferent vagal signaling

PGE2 produced in the periphery triggers the early phase of the febrile response to infection and may contribute to later phases. It can be hypothesized that peripherally synthesized PGE2 transmits febrigenic signals to the brain via vagal afferent nerves. Before testing this hypothesis, we investigated whether the febrigenic effect of intravenously administered PGE2 is mediated by the brain and is not the result of a direct action of PGE2 on thermoeffectors. In anesthetized rats, intravenously injected PGE2 (100 microg/kg) caused an increase in sympathetic discharge to interscapular brown adipose tissue (iBAT), as well as increases in iBAT thermogenesis, end-expired CO2, and colonic temperature (Tc). All these effects were prevented by inhibition of neuronal function in the raphe region of the medulla oblongata using an intra-raphe microinjection of muscimol. We then asked whether the brain-mediated PGE2 fever requires vagal signaling and answered this question by conducting two independent studies in rats. In a study in anesthetized rats, acute bilateral cervical vagotomy did not affect the effects of intravenously injected PGE2 (100 microg/kg) on iBAT sympathetic discharge and Tc. In a study in conscious rats, administration of PGE2 (280 microg/kg) via an indwelling jugular catheter caused tail skin vasoconstriction, tended to increase oxygen consumption, and increased Tc; none of these responses was affected by total truncal subdiaphragmatic vagotomy performed 2 wk before the experiment. We conclude that the febrile response to circulating PGE2 is mediated by the brain, but that it does not require vagal afferent signaling.     

Cough and laryngeal muscle discharges in brainstem lesioned anaesthetized cats

Experiments were carried out to determine whether there are separate drives from the selected neuronal networks of the brainstem affecting the discharge patterns of laryngeal and respiratory pump muscles during cough. Twenty-four non-decerebrate spontaneously breathing cats anesthetized with sodium pentobarbitone were used. Microinjections of kainic acid into the lateral tegmental field of the medulla, medullary midline or pontine respiratory group eliminated the cough evoked by mechanical stimulation of the tracheobronchial and laryngopharyngeal mucosa. These stimuli, in most cases, provoked irregular bursts of discharges in the posterior cricoarytenoid and thyroarytenoid laryngeal muscles (or they had no effect on them). No pattern of laryngeal muscle activities following lesions resembled the laryngeal cough response. Lesions of the target regions did not result in any apparent changes in the eupnoeic pattern of laryngeal activity. Neurons of the medullary lateral tegmental field, raphe nuclei and the pontine respiratory group seem to be indispensable for the configuration of the central cough motor pattern. However, these neurons do not appear to be essential for the discharge patterns of laryngeal motoneurons during eupnoea. The residual laryngeal "cough" responses are probably mediated by an additional motor drive.     

Neuronal correlates of the activation of the brain-reinforcing system in dogs

In analysis of neuronal activity of g. proreus of dogs brain in response to positive and differentiation conditioned cutaneous stimuli, in 44% of 78 studied neurons "late responses" appeared in the form of impulse activity intensification elicited by a positive conditioned stimulus after the end of eating and by a differentiation one--during conditioned signal action; it persisted in different neurones for 30--60 s. By means of various functional tests it has been shown that these reactions are a neurophysiological correlate of animals emotional state gradient.     

A neurobehavioral model for rapid actions of corticosterone on sensorimotor integration.

Stress-induced corticosterone (CORT) secretion that causes a rapid blockade of courtship clasping by male roughskin newts (Taricha granulosa) is mediated by a specific neuronal membrane receptor for CORT. Amplectic clasping, which can be triggered by pressure on the ventral body surface and cloaca, is controlled by the influence of medullary neurons on the spinal cord. Using clasping as a simple neurobehavioral model, we have focused our analysis of CORT effects on clasping by examining the steroid's effects on neurophysiological properties of medullary neurons, especially medullary reticulospinal neurons, the principal output cells from the brain to the spinal cord. Systemic CORT caused, within 3 min of injection, diverse reductions in reticulospinal neuron excitability. Another rapid CORT effect on medullary neurons was to depress responsiveness to pressure on the cloaca. Experiments with chronically implanted, freely moving newts revealed that the rapid CORT effects are quite specific to neural processes related to clasping. CORT injections rapidly blocked clasping in response to cloacal stimuli and concurrently depressed neuronal responses to cloacal pressure and firing associated with clasping. Activity of reticulospinal neurons was often associated with nonclasping movements and this activity was rarely altered by CORT. Thus, CORT mainly affected aspects of neuronal function related to clasping. In other neurophysiological experiments, we found that the neuropeptides vasotocin and corticotropin-releasing hormone modified the neural effects of CORT. Prior exposure of medullary neurons to either of these neuropeptides caused systemic CORT administration to rapidly potentiate neuronal responses to cloacal stimuli, indicating that the direction and potency of CORT effects depend critically on the prevailing neuroendocrine state of the brain.