Prostaglandin E2 fever mediated by inhibition of the GABAergic transmission in the region immediately adjacent to the organum vasculosum of the lamina terminalis

Unilateral microinjection of prostaglandin (PG)E(2) into a region immediately adjacent to the organum vasculosum of the lamina terminalis (peri-OVLT) in the preoptic area elicited thermogenic, tachycardic, cutaneous vasoconstrictive, and hyperthermic responses simultaneously in urethane-chloralose-anesthetized rats. The magnitude of these responses increased dose-dependently over the range of 57 fmol-2.8 pmol, except for the vasoconstrictive response. Microinjection of a GABA(A) receptor antagonist, bicuculline methiodide or gabazine (5-20 pmol), into the PGE(2)-sensitive site in the peri-OVLT region also elicited responses similar to those induced by PGE(2). Although administration of a GABA(A) receptor agonist, muscimol (10 pmol), microinjected into the same site alone usually had no effect on the rate of whole-body O(2) consumption, heart rate or colon and skin temperatures, all PGE(2)-induced responses were blocked 10 min after the muscimol pretreatment and recovered at 50-90 min. Pretreatment with the vehicle, saline, had no effect on the PGE(2)-induced responses. These results suggest that spontaneous release of GABA and tonic activation of GABA(A) receptors in the peri-OVLT region prevent the elevation in the body core temperature under normal circumstances and that PGE(2)-induced febrile responses are mediated, at least in part, by inhibition of the GABAergic transmission in this area.     

The role of orexin-1 receptors in physiologic responses evoked by microinjection of PgE2 or muscimol into the medial preoptic area

The medial preoptic area (mPOA) of the hypothalamus has long been thought to play an important role in both fever production and thermoregulation. Microinjections of prostaglandin E2 (PgE2) or the GABA(A) agonist muscimol into the mPOA cause similar increases in body temperature, heart rate, and blood pressure. Microinjections of these compounds however evoke different behavioral responses with muscimol increasing and PgE2 having no effect on locomotion. The purpose of this study was to determine the role of orexin-1 receptors in mediating these dissimilar responses. Systemic injections of the orexin-1 receptor antagonist SB-334867 reduced temperature and cardiovascular responses produced by microinjections of muscimol, but had no effect on either response produced by PgE2. SB-334867 did not significantly decrease locomotion evoked by microinjections of muscimol into the mPOA. These data suggest that there are two central nervous system circuits involved in increasing body temperature, heart rate and blood pressure: one circuit activated by muscimol, involving orexin neurons, and a separate orexin-independent circuit activated by PgE2.     

Negligible role of catecholaminergic receptors in the anteroventral third ventricular region in mediating vasopressin-releasing and cardiovascular actions of prostaglandin E2

The aim of this study was to pursue the roles of the catecholamine receptors in the anteroventral third ventricular region (AV3V), a cerebral site engaged in various stress responses, in prostaglandin (PG) E₂-evoked vasopressin (AVP) release and cardiovascular action. Experiments were conducted in conscious rats in which cerebral and vascular cannulae had been implanted chronically. Local infusion (0.5 μl, 1 min) of dopamine (150 nmol), a D₁-dopaminergic agonist SKF 38393 (17 nmol) and an α-adrenergic agonist phenylephrine (150 nmol), as well as PGE₂ (7 nmol), into the AV3V enhanced plasma AVP 5 min later, without affecting plasma osmolality and electrolytes. In contrast to the increases in both arterial pressure and heart rate observed when PGE₂ was applied, dopamine and SKF 38393 did not affect these variables, and phenylephrine elevated only arterial pressure. The AV3V infusion of a β-agonist isoproterenol (100 nmol) did not change plasma AVP, although it decreased arterial pressure and increased heart rate. The increase in plasma AVP by dopamine was not blocked by the preinfusion of the D₂-antagonist sulpiride (13 nmol) into the AV3V 10 min before, but was abolished by that of the D₁-antagonist SCH-23390 (8 nmol). The effects of phenylephrine on both plasma AVP and the blood pressure were prevented by the preadministration of the α-antagonist phenoxybenzamine (13 nmol). However, the pretreatments with phenoxybenzamine, sulpiride or SCH 23390 did not inhibit the responses of AVP, arterial pressure and heart rate caused by PGE₂. These antagonists were without significant effect on AVP and other variables when given alone. The infusion sites of PGE₂ and the other drugs identified histologically included the AV3V structures such as the organum vasculosum laminae terminalis or its vicinity, median preoptic nucleus, medial preoptic nucleus and periventricular hypothalamic nucleus. Dopamine or phenylephrine administered into the cerebral ventricle at the same dose as used in the AV3V application did not exert a significant effect on plasma AVP, arterial pressure and heart rate. These results suggest that catecholamine receptors in the AV3V may not be involved in the AVP-secreting, tachycardiac and pressor responses evoked by topical action of PGE₂ on this area, despite their ability to influence hormone release and cardiovascular function. Received: 3 November 1998 / Accepted: 7 July 1999     

Microinjection of muscimol into raphe pallidus suppresses tachycardia associated with air stress in conscious rats

Sympathetically mediated tachycardia is a characteristic feature of the physiological response to emotional or psychological stress in mammals. Activation of neurons in the region of the dorsomedial hypothalamus appears to play a key role in the integration of this response. Tachycardia evoked by chemical stimulation of the dorsomedial hypothalamus can be suppressed by microinjection of the GABA_A receptor agonist and neuronal inhibitor muscimol into the raphe pallidus (RP). Therefore, we tested the hypothesis that neuronal excitation in the RP mediates tachycardia seen in experimental air stress in rats. Microinjection of the GABA_A receptor antagonist bicuculline methiodide (BMI) into the RP evoked increases in heart rate. At the same sites, microinjection of muscimol (80 pmol (100 nl)⁻¹) had no effect on heart rate under baseline conditions but virtually abolished air stress-induced tachycardia, while microinjection of lower doses (10 or 20 pmol) produced transient but clear suppression. Microinjection of muscimol at sites outside the RP had no effect on stress-induced tachycardia, although modest suppression was apparent after injection at two sites within 500 μm of the RP. In another series of experiments, microinjection of muscimol (80 pmol (100 nl)⁻¹) into the RP failed to influence the changes in heart rate produced by baroreceptor loading or unloading. These findings indicate that activity of neurons in the RP plays a previously unrecognized role in the generation of stress-induced tachycardia.     

Behavioural and autonomic induction of prostaglandin E-1 fever in squirrel monkeys.

1. Prostaglandins E1 (PGE1) was injected into the preoptic/anterior hypothalamic (PO/AH) area of the squirrel monkey. 2. Increases in rectal temperature (Tre) produced by PGE1 injections of 20 ng to 500 ng were dose-dependent. 3. When ambient temperature (Ta) was below the thermoneutral zone, increases in Tre were produced entirely by increases in metabolic rate. With Ta at the upper end of the thermoneutral zone, increases in Tre were produced by vasoconstriction in addition to lesser increases in metabolic rate. 4. During sessions of behavioural temperature regulation, PGE1 injections were followed by the selection of a higher Ta, increased skin temperature and subsequent increases in Tre. 5. PGE1 injections produce dose-dependent increases in Tre which are similar regardless of ambient temperature or whether behavioural or autonomic means are utilized to raise the heat content of the body.     

Excitatory amino acid receptor activation in the raphe pallidus area mediates prostaglandin-evoked thermogenesis

To investigate the role of excitatory amino acid neurotransmission within the rostral raphe pallidus area (RPa) in thermogenic and cardiovascular responses, changes in sympathetic nerve activity to brown adipose tissue (BAT), BAT temperature, expired CO(2), arterial pressure, and heart rate were recorded after microinjection of excitatory amino acid (EAA) receptor agonists into the RPa in urethan-chloralose-anesthetized, ventilated rats. To determine whether EAA neurotransmission within the RPa is necessary for the responses evoked by disinhibition of the RPa or by prostaglandin E(2) acting within the medial preoptic area, BAT sympathetic nerve activity, BAT temperature, expired CO(2), arterial pressure, and heart rate were measured during these treatments both before and after blockade of EAA receptors within the RPa. Microinjection of EAA receptor agonists into the RPa resulted in significant increases in all measured variables; these increases were attenuated by prior microinjection of the respective EAA receptor antagonists into the RPa. Microinjection of prostaglandin E(2) into the medial preoptic area or microinjection of bicuculline into the RPa resulted in respective significant increases in BAT sympathetic nerve activity (+approximately 190% and +approximately 235% of resting levels), in BAT temperature (approximately 1.8 degrees C and approximately 2 degrees C), in expired CO(2) (approximately 1.1% and approximately 1.1%), and in heart rate (approximately 97 beats per minute (bpm) and approximately 100 bpm). Blockade of ionotropic EAA receptors within the RPa by microinjection of kynurenate completely reversed the prostaglandin E(2) or bicuculline-evoked increases in all of the measured variables. Blockade of either N-methyl-D-aspartate (NMDA) receptors or non-NMDA receptors alone resulted in marked attenuations of the prostaglandin E(2)-evoked effects on all of the measured variables. These data demonstrate that activation of an EAA input to the RPa is necessary for the BAT thermogenic and the cardiovascular effects resulting from the actions of prostaglandin E(2) within the medial preoptic area or from the disinhibition of local neurons in the RPa.     

Raphe pallidus neurons mediate prostaglandin E2-evoked increases in brown adipose tissue thermogenesis

To elucidate central neural pathways contributing to the febrile component of the acute phase response to pyrogenic insult, I sought to determine whether activation of neurons in the rostral raphe pallidus (RPa) is required for the increase in brown adipose tissue (BAT) thermogenesis evoked by i.c.v. prostaglandin E(2) (PGE(2)) in urethane-chloralose-anesthetized, ventilated rats. BAT sympathetic nerve activity (SNA; +224% of control), BAT temperature (+1.8 degrees C), expired CO(2) (+1.3%), mean arterial pressure (+23 mm Hg), and heart rate (+73 beats per minute) were significantly increased after i.c.v. PGE(2) (2 microg). Microinjection of either the GABA(A) receptor agonist, muscimol (2 mM, 60 nl), or glycine (0.5M, 60 nl) into RPa resulted in a prompt reversal of the PGE(2)-evoked stimulation of BAT SNA, BAT thermogenesis and heart rate, with these variables returning to control levels prior to i.c.v. PGE(2) following the long-lasting, muscimol-induced inhibition of RPa neurons. In conclusion, activation of neurons in RPa, possibly BAT sympathetic premotor neurons, is essential for the increases in BAT SNA and BAT thermogenesis stimulated by i.c.v. administration of PGE(2). The increased heart rate likely contributing to an augmented cardiac output supporting the increased BAT thermogenesis in response to PGE(2) is also dependent on neurons in RPa. These results contribute to our understanding of central neural substrates for the augmented thermogenesis during fever.     

Effect of pyrogen and antipyretics on prostaglandin acitvity in cisternal c.s.f. of unanaesthetized cats

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 PGE(1)-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 PGE(1)-like activity was detected, or its activity was low. Higher values were obtained in only a few cats.3. In each experiment the PGE(1)-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 PGE(1)-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 PGE(1)-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.     

Hemodynamic and plasma catecholamine responses to hyperthermic cancer therapy in humans.

Cancer patients, treated with hyperthermia (to 41.5 degrees C) under thiopental and fentanyl anesthesia, had smaller increases in heart rate and cardiac index and lesser decreases in mean arterial pressure than those reported in normal volunteers. At basal body temperature anesthesia did not alter catecholamine levels. Increasing body temperature to 39.5 degrees C and 41.5 degrees C resulted in parallel increases in heart rate and cardiac index that were directly related to the increases in plasma norepinephrine levels. At basal temperature cutaneous venous plasma norepinephrine levels exceeded those of arterial; mixed-venous plasma levels were intermediate. At 39.5 degrees C and 41.5 degrees C there were sequential increases in plasma norepinephrine. The increases in mixed-venous and arterial norepinephrine were significantly greater than in cutaneous venous blood. The differential increases in norepinephrine levels in cutaneous venous, mixed-venous, and arterial blood indicate that during hyperthermia sympathetic nerve activity in skin is decreased while that in other areas is increased, suggesting that alterations in sympathetic activity modulate the hemodynamic changes that attend hyperthermia in man.     

Psychologic stress increases plasma levels of prolactin, cortisol, and POMC-derived peptides in man

Stressful social interactions have been shown to elicit increases in heart rate as well as in plasma levels of epinephrine, norepinephrine, and cortisol in humans. We sought to determine whether a competitive oral examination would affect plasma levels of the pituitary hormones ACTH, beta-endorphin, beta-lipotrophic hormone, and prolactin in a group of healthy young males. Seven min after beginning the examination, heart rate increased 27% and plasma levels of ACTH, beta-endorphin, beta-lipotropic hormone and prolactin rose 59%, 79%, 42%, and 46%, respectively, compared to values shortly before the examination. These hormone values returned to initial levels after the subjects returned to the waiting room. Plasma cortisol changes were similar in direction to those of ACTH but occurred about 15 min later. The present study demonstrates that a stressful social interaction can elicit rapid increases in plasma levels of the proopiomelanocortin derived peptide hormones and prolactin in man.     

Heat loss responses and blockade of prostaglandin E2-induced thermogenesis elicited by α1-adrenergic activation in the rostromedial preoptic area

The unilateral microinjection of noradrenaline (NA), but not vehicle solution, into the rostromedial preoptic area (POA) elicited simultaneous increases in cutaneous temperatures of the tail and sole of the foot and decreases in the whole-body O₂ consumption rate, heart rate, and colonic temperature in urethane–chloralose-anesthetized rats, suggesting a coordinate increase in heat loss and decrease in heat production. The magnitude of these responses increased dose-dependently over the range of 1–100 pmol, except for the metabolic and bradycardic responses. Similar hypothermic responses were elicited by the microinjection of 40 pmol methoxamine (an α₁-adrenergic agonist), but not by that of clonidine (an α₂-agonist) or isoproterenol (a β-agonist). Sites at which microinjection of NA elicited hypothermic responses were in the vicinity of the organum vasculosum of the lamina terminalis including the median preoptic nucleus, whereas no thermal or metabolic response was elicited when NA was microinjected into the lateral POA or caudal part of the medial POA. The microinjection of 130 fmol prostaglandin (PG) E₂ into the NA-sensitive site always elicited thermogenic, tachycardic, and hyperthermic responses. Furthermore, the PGE₂-induced febrile responses were greatly attenuated by prior administration of NA at the same site. These results demonstrate that NA in the rostromedial POA exerts α₁-adrenoceptor-mediated hypothermic effects and opposes PGE₂-induced fever.     

Sexual behavior of male rats is differentially affected by timing of perinatal ACTH administration.

The laboratory rat was used as a model to investigate the effect of pre- and/or postnatal ACTH administration on sexual differentiation of the brain. Pregnant Sprague-Dawley rats were injected with ACTH 1-24 (10 micrograms/kg/2x/day or 500 micrograms/kg/2x/day); postnatally treated neonates were injected with the above dosages once a day. Perinatal treatment with ACTH (10 micrograms/kg/2x/day) altered several sexual behavior measurements, but did not have an overall effect on the number of males that exhibited sexual behavior. At a higher dose (500 micrograms/kg/2x/day) prenatal ACTH administration decreased sexual behavior in male rats, as measured by an increase in the percent of males that did not mount or intromit. In contrast, all males treated postnatally with ACTH (500 micrograms/kg/2x/day) completed 2 ejaculatory series and initiated a third series. No significant differences were observed in adult plasma testosterone or prolactin levels; however, serotonin levels in the preoptic area of adult male rats treated prenatally with ACTH (500 micrograms/kg/2x/day) were significantly higher than in prenatally treated saline males. In addition, an increase in plasma ACTH in adulthood was observed in animals injected postnatally with saline. This study indicates that the decrease in sexual behavior observed in males treated prenatally with ACTH is associated with increased serotonin levels in the preoptic area, which suggests that ACTH may act as a neuromodulator during sexual differentiation of the brain. It also demonstrates that the effect of perinatal manipulations on the development of male sexual behavior may vary depending on the ontogenetic period of the brain.     

Longer term progesterone treatment induces changes of GABAA receptor levels in forebrain sites in the female hamster: quantitative autoradiography study

Summary Quantitative receptor autoradiography was applied to evaluate the effects of one and three injections of 1 mg progesterone (P) on ³H muscimol binding levels in the different forebrain areas of the female hamster. The overall effect of P resulted in substantial increases in ³H muscimol binding in brain areas containing gonadal steroid receptors: medial preoptic area and ventromedial hypothalamic nucleus as well as in bed nucleus stria terminalis and subiculum. Similarly, the caudate putamen, a region where gonadal steroid receptors are not abundant, also showed substantial increases of ³H muscimol binding receptor levels. Moreover, female hamsters treated with P for 3 days presented altered ³H muscimol binding levels in the amygdala and thalamic nucleus that were, in some cases, not produced by one dose of P. P treatment also decreased GABA_A binding in two areas of the thalamus. These results are consistent with the proposal that P may alter GABAergic inhibitory activity via changes in the levels of GABA_A receptors in certain forebrain areas in the female hamster, changes which may be linked to the mediation of anxiolytic effects and to the inhibition of aggressive behavior. These data also suggest that P treatment increases the binding of high affinity GABA receptors in some forebrain sites and may be responsible for maintenance of the anxiolytic effects.     

Synergistic interactions between airway afferent nerve subtypes regulating the cough reflex in guinea-pigs

In urethane–chloralose anaesthetized, neuromuscularly blocked, artificially ventilated rats, we demonstrated that activation of carotid chemoreceptors inhibits the elevated levels of brown adipose tissue (BAT) sympathetic nerve activity (SNA) evoked by hypothermia, by microinjection of prostaglandin E₂ into the medial preoptic area or by disinhibition of neurones in the raphe pallidus area (RPa). Peripheral chemoreceptor stimulation with systemic administration of NaCN (50 μg in 0.1 ml) or with hypoxic ventilation (8% O₂–92% N₂, 30 s) completely inhibited BAT SNA. Arterial chemoreceptor-evoked inhibition of BAT SNA was eliminated by prior bilateral transections of the carotid sinus nerves or by prior inhibition of neurones within the commissural nucleus tractus solitarii (commNTS) with glycine (40 nmol/80 nl) or with the GABA_A receptor agonist muscimol (160 pmol/80 nl; 77 ± 10% attenuation), or by prior blockade of ionotropic excitatory amino acid receptors in the commNTS with kynurenate (8 nmol/80 nl; 82 ± 10% attenuation). Furthermore, activation of commNTS neurones following local microinjection of bicuculline (30 pmol/60 nl) completely inhibited the elevated level of BAT SNA resulting from disinhibition of neurones in the RPa. These results demonstrate that hypoxic stimulation of arterial chemoreceptor afferents leads to an inhibition of BAT SNA and BAT thermogenesis through an EAA-mediated activation of second-order, arterial chemoreceptor neurones in the commNTS. Peripheral chemoreceptor-evoked inhibition of BAT SNA could directly contribute to (or be permissive for) the hypoxia-evoked reductions in body temperature and oxygen consumption that serve as an adaptive response to decreased oxygen availability.     

Dose-dependence of bacterial lipopolysaccharide (LPS) effects on peak response and time course of the immune-endocrine host response in humans

OBJECTIVE AND DESIGN: Dose-dependence of lipopolysaccharide (LPS) effects on peak and time course parameters of the immune-endocrine host response was examined in a placebo-controlled design. SUBJECTS: Data from 42 male volunteers were included. TREATMENT: 0.4 or 0.8 ng LPS/kg body weight were applied at 7.00 p.m. METHODS: Body temperature, heart rate and leukocyte counts were quantified. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), adrenocorticotropic hormone (ACTH), cortisol and human growth hormone (hGH) were measured. RESULTS: LPS increased significantly the levels of immune (TNF-alpha, IL-6) and endocrine (ACTH, cortisol) parameters. HGH secretion was advanced without changes in the total amount of hGH released. Dose-dependence of endotoxin's effects was significant for neuroendocrine (cortisol) and physiological (temperature, heart rate) parameters. Examination of time course parameters demonstrated that the higher dose of endotoxin prolonged the increases in temperature, IL-6 and cortisol levels. CONCLUSIONS: Our data show that increases in the dosage of LPS lead to differential peak responses and changed time course patterns of the human host response.     

Assessing the role of the medial preoptic area in ethanol-induced hypothermia

Administration of ethanol produces hypothermia. The preoptic area/anterior hypothalamus (POA/AH) contains warm- and cold-sensitive neurons that are important for temperature regulation. The present study evaluated the effect of ethanol on Fos immunoreactivity (Fos-ir) in the medial preoptic area (MPOA) and the effect of lesions to the MPOA on ethanol-induced hypothermia. Rats receiving 1.5-g/kg ethanol showed an increase in Fos-ir in the MPOA. However, lesions to the MPOA did not affect core body temperature. These findings indicate that ethanol increases neural activity in the MPOA, but this increased activity does not influence ethanol-induced changes in core body temperature.     

Effect of atrial natriuretic factor on renal prostaglandin E2 release in the anaesthetized dog.

Experiments were undertaken in two groups of barbiturate anaesthetized dogs to examine whether atrial natriuretic factor (ANF) exerts an effect on renal release of prostaglandin E2 (PGE2). In the first group, intravenous infusion of ANF (50 ng min-1 kg-1 body wt) reduced basal PGE2 release from 4.4 +/- 0.8 pmol min-1 to 1.8 +/- 0.7 pmol min-1. In the second group, intrarenal infusion of an alpha 1-adrenoceptor agonist, phenylephrine (2.5-6.75 micrograms min-1), raised PGE2 release from 2.7 +/- 0.5 pmol min-1 to 7.5 +/- 1.3 pmol min-1. During continuous alpha 1-adrenergic stimulation, intravenous infusion of ANF (100 ng min-1 kg-1 body wt) reduced PGE2 release to 3.5 +/- 1.0 pmol min-1. These results demonstrate that ANF reduces basal and alpha 1-adrenergic stimulated renal PGE2 release.     

Activation of lateral hypothalamic neurons stimulates brown adipose tissue thermogenesis

The lateral hypothalamic area, containing orexin neurons, is involved in several aspects of autonomic regulation, including thermoregulation and energy expenditure. To determine if activation of lateral hypothalamic area neurons influences sympathetically-regulated thermogenesis in brown adipose tissue, we microinjected bicuculline (120 pmol, 60 nl, unilateral) into the lateral hypothalamic area in urethane/chloralose-anesthetized, artificially-ventilated rats. Disinhibition of neurons in lateral hypothalamic area evoked a significant increase (+1309%) in brown adipose tissue sympathetic nerve activity accompanied by parallel increases in brown adipose tissue temperature (+2.0 degrees C), in expired CO2 (+0.6%), in heart rate (+88 bpm) and in mean arterial pressure (+11 mm Hg). Subsequent microinjections of glycine (30 nmol, 60 nl) to inhibit local neurons in raphe pallidus or in dorsomedial hypothalamus or of glutamate receptor antagonists into dorsomedial hypothalamus promptly reversed the increases in brown adipose tissue sympathetic nerve activity, brown adipose tissue temperature and heart rate evoked by disinhibition of neurons in lateral hypothalamic area. We conclude that neurons in the lateral hypothalamic area can influence brown adipose tissue sympathetic nerve activity, brown adipose tissue thermogenesis and heart rate through pathways that are dependent on the activation of neurons in dorsomedial hypothalamus and raphe pallidus.     

Respiratory and body temperature modulation by adenosine A1 receptors in the anteroventral preoptic region during normoxia and hypoxia

The present study was undertaken to investigate adenosine as a simultaneous mediator of hypoxia-induced hyperventilation and regulated hypothermia in the anteroventral preoptic region (AVPO), the thermointegrative region of the central nervous system (CNS). Accordingly, we predicted that injection of aminophylline and DPCPX, non-selective and A(1) receptor antagonists, respectively, into the AVPO would exacerbate the ventilatory response and lessen the drop in body temperature (T(b)) caused by hypoxia. We measured ventilation (V ) and T(b) of conscious Wistar rats before and after AVPO injection of aminophylline (1 and 10 microg/100 nL) or DPCPX (17.5 and 175 ng/100 nL), or their respective vehicles, followed by 30 min of hypoxia (7% O(2)). Vehicles and the lower doses of both antagonists had no effect on V and T(b) during normoxia or hypoxia. The higher doses of aminophylline and DPCPX increased (P<0.05) the hypoxia-induced hyperventilation, whereas the drop in T(b) elicited by hypoxia was attenuated (P<00.05) by DPCPX only. This higher DPCPX dose also increased T(b) during normoxia. The present data is consistent with the notion that adenosine plays an inhibitory role in respiratory and metabolic regulation, in a way that A(1) receptors stimulation in the AVPO inhibits ventilatory drive during hypoxia and tonically modulates basal T(b).     

Selective effects of beta-endorphin infused into the hypothalamus, preoptic area and bed nucleus of the stria terminalis on the sexual and ingestive behaviour of male rats

beta-Endorphin was infused bilaterally into the medial preoptic area-anterior hypothalamic continuum at doses of 5, 10 and 40 pmol each side. The highest dose selectively abolished mounting, intromitting and ejaculating in sexually experienced male rats paired with an oestrous female. Males infused with 40 pmol beta-endorphin still followed the female, investigated her anogenital region and other parts of her body, but made abortive attempts to mount. A dose of 5 pmol beta-endorphin had no effect, but 10 pmol proved partially effective. The same males, in other tests, were allowed to ingest a highly preferred, sweet, non-calorific solution (acesulfame-K) in the absence of a female. beta-Endorphin infusions (up to 40 pmol) into the same area of the hypothalamus had no effect on this behaviour. Control males allowed simultaneous access both to an oestrous female and to the sweet solution copulated normally but reduced their ingestive behaviour, despite there being sufficient time during tests for both to occur. beta-Endorphin (40 pmol) infused into the preoptic area-anterior hypothalamic continuum under these conditions suppressed sexual interaction, but ingestion of acesulfame-K increased to values observed when the female was absent. beta-Endorphin infused into neighbouring areas of the brain had different behavioural effects. Sexual behaviour was not inhibited, and ingestion of acesulfame-K was unaltered, when beta-endorphin was infused either into the bed nucleus of the stria terminalis or the rostral ventromedial hypothalamus. However, infusions of cholecystokinin-8 into the ventromedial hypothalamus suppressed acesulfame-K ingestion in most animals, showing that the cannulae were placed in an area regulating ingestive behaviour. The inhibition of sexual behaviour after preoptic area-anterior hypothalamic continuum infusions of beta-endorphin was prevented by either pretreating rats with 1 mg/kg naloxone intraperitoneally, or by infusing a putative delta opiate receptor blocker (0.5 pmols ICI 174864) into the preoptic area-anterior hypothalamic continuum 5 min prior to beta-endorphin treatment. ICI 174864 administered alone significantly increased mount rate and reduced the post-ejaculatory refractory period in copulating males. These experiments suggest that there is both neurochemical and neuroanatomical specificity relating beta-endorphin to sexual behaviour in the male rat.