氨甲酰胆碱引起的促钠排泄与下丘脑TH—IR神经元活性的变化

目的：我们最近的实验发现大鼠侧脑室注射氨甲酰胆碱引起显著的促钠排泄作用,本工作同时还观察了下丘脑内不同脑区的儿茶酚胺能神经元活性的变化。方法和结果：氨甲酰胆碱注射后４０ｍｉｎ,下丘脑室旁核的腹侧和内侧小细胞部、内侧视前区、尾核、苍白球的酪氨酸羟化酶免疫反应（ｔｈｙｒｏｓｉｎｅｈｙｄｒｏｘｙｌａｓｅｉｍｍｕｎｏｒｅａｃｔｉｖｉｔｙ,ＴＨＩＲ）阳性细胞数减少,免疫反应染色强度降低;下丘脑室旁核的后部,下丘脑前区的后部、下丘脑室周核、弓状核、下丘脑外侧区的ＴＨＩＲ阳性细胞数增多,免疫反应染色强度增强。结论：侧脑室注射氨甲酰胆碱对脑内不同脑区的内源性儿茶酚胺能神经元分别有兴奋或抑制作用,其与促钠排泄的关系将在本文中讨论     

Hyperthermic effect of a trypsin inhibitor in rats and rabbits

The influence of intraventricular and intravenous administration of trypsin inhibitor (from soya-bean) on the body temperature was studied in experiments on unanesthetized rats and rabbits. It was established that the substance provoked a steady and prolonged hyperthermia in rats and rabbits, attenuated by pre-administration of sodium salicylate. Hyperthermia was accompanied by a significant decrease in the content of PGE2 in the hypothalamus. The results suggest than inhibition of certain trypsin-like serine proteases in thermoregulatory centres may be one of the factors responsible for the development of fever.     

Effect of arecoline on neuronal activity in the posterior hypothalamus of rabbits with experimental fever

It has been found in experiments on unanesthetized rabbits that arecoline administered to the lateral ventricle of the brain produced an action which was opposite to that of leukocytic pyrogen. It inhibited the activity of individual neurons of the posterior hypothalamus and decreased the body temperature, with this decrease being attended by the signs of intensified heat emission. Arecoline injection coupled with the central action of PGE2 was followed by an increase in the neuronal activity in the posterior hypothalamus and reduction of hyperthermal response.     

吗啡和纳洛酮对损毁下丘脑诱致的大鼠胃粘膜损伤之影响

本实验观察了静注吗啡和纳洛酮对电解损毁后部下丘脑诱致的大鼠胃粘膜损伤的影响并观察了在静注吗啡、纳洛酮后和侧脑室注射纳洛酮后其胃酸分泌和血清胃泌素水平之变化。实验揭示,吗啡仅略为降低该神经源性胃粘膜损伤程度,而纳洛酮则明显地减少其胃粘膜损伤;静注吗啡能抑制后部下丘脑损毁后大鼠的胃酸分泌,增加其血清胃泌素水平,而静注纳络酮后,这种大鼠的胃酸分泌增加,但血清胃泌素水平无明显变化;侧脑室注射纳洛酮对后部下丘脑损毁后大鼠胃酸分泌和血清胃泌素水平无明显影响。本结果表明,胃酸可能是导致这种消化道损伤的条件之一,而不是最重要因素;静注纳洛酮对后部下丘脑损毀后大鼠胃粘膜变化有保护作用。后者提示,内源性阿片样肽可能参与这种神经源性胃粘膜损伤的形成。     

Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia

Mu-opioid receptor activation increases body temperature and affects cardiovascular function. In the present study, fentanyl was administered intravenously [100 mug/kg (300 nmol/kg) iv] and intracerebroventricularly [3.4 mug (10 nmol) in 10 microl icv] in urethane-chloralose-anesthetized, artificially ventilated rats. Increases in brown adipose tissue (BAT) sympathetic nerve activity (SNA) (peak, +326% of control), BAT temperature (peak, +0.8 degrees C), renal SNA (peak, +146% of control), and heart rate (HR; peak, +32 beats/min) produced by intravenous fentanyl were abolished by premamillary transection of the neuraxis but were mimicked by intracerebroventricular administration of fentanyl, which also increased arterial pressure (AP; peak, +12 mmHg). Pretreatment with the opioid antagonist naloxone (100 nmol in 10 microl icv) eliminated the intracerebroventricular fentanyl-evoked responses. Microinjection of glycine (0.5 M, 60 nl) to inhibit local neurons in the rostral raphe pallidus (RPa) selectively reversed the intracerebroventricular fentanyl-evoked increases in BAT SNA and HR, while the fentanyl-evoked excitation in RSNA, the pressor responses, and the tachycardic responses were reversed by inhibition of neurons in the rostral ventrolateral medulla (RVLM). Prior inhibition of neurons in the dorsomedial hypothalamus eliminated the intracerebroventricular fentanyl-evoked increases in BAT SNA, BAT temperature, and HR, but not those in RSNA or AP. These results indicate that activation of central mu-opioid receptors with fentanyl can elicit BAT thermogenesis and cardiovascular stimulation through excitation of the sympathetic outflows to BAT, kidney, and heart. Activation of neurons in the rostral RPa and RVLM are essential for the increases in BAT thermogenesis and renal sympathoexcitation, respectively, induced by activation of central mu-opioid receptors. BAT thermogenesis could contribute to fentanyl-evoked hyperthermia, particularly in infants where BAT plays a significant role in thermoregulation.     

The effect of porcine Orexin A on insulin plasma concentrations in pigs

Orexin A is a member of a wider family of orexigenic neuropeptides that have been recently discovered. They are produced by a small group of neurons located in the area of the brain, round the nucleus of the fornix (posterior hypothalamus), in the paraventricular nucleus, the dorsomedial nucleus, the ventromedial hypothalamus, as well as in the lateral hypothalamic region; these are sites that are known to be involved in regulating feeding in mammals. Orexin A is a neuropeptide, which is involved in appetite regulation and energy homeostasis. An intracerebroventricular (i.c.v.) injection of Orexin A in the brain of rats causes an impressive increase in food consumption. In addition, a subcutaneous or intravenous (IV) injection of Orexin A produces changes on insulin plasma concentrations in rats. Recent research suggests that Orexin A is also involved in regulating many other physiological functions. In this study, we examined the potential effects of the central administration of porcine Orexin A on insulin plasma concentrations in pigs, and whether these changes are connected with the possible effect of the neuropeptide on the enteroinsular axis.     

Effect of oxytocin on the activity of posterior hypothalamic neurons in the rat

Changes of unit activity in different nuclei of the posterior hypothalamus induced by intravenous oxytocin injections were studied in acute experiments on Wistar rats anaesthetized with nembutal. Influence of nonapeptide was dose-dependent. Latencies of various neuronal reactions were different. Mechanisms of oxytocin regulation of neuronal activity in the posterior hypothalamus are discussed.     

Substance P as a factor enhancing resistance of the surfactant lung system to chronic immobilization stress

In chronic experiments on non-line white rats the influence of system (intraperitoneal) and central (into the lateral brain ventricle) administration of substance P on lung surfactant system was studied in stressed and non-stressed animals. A single injection of substance P limited pulmonary surfactant activity disorders in immobilisation stress. Stress-induced increase of phospholipids level in broncho-alveolar lavage fluid remained the same in intracerebroventricular administration and was partly reduced in intraperitoneal one. In intact rats, a single injection of peptide was accompanied by alveolar phospholipids accumulation. In rabbits, multiple intracerebroventricular injections of substance P enhanced the opposite effect.     

Jejunal administration of linoleic acid increases activity of neurons in the paraventricular nucleus of the hypothalamus

The present experiment examined whether neurons located in the paraventricular nucleus of the hypothalamus (PVN) respond to intestinal infusions of long-chain fatty acids. Single-unit recordings were made of neurons located in and adjacent to the PVN during jejunal administration of linoleic acid. Jejunal administration of linoleic acid increased single-unit activity of neurons located in the PVN but did not affect activity of neurons located in adjacent tissue outside the PVN. The largest increases in neuronal activity were observed in the anterior PVN (0.9-1.3 mm posterior to bregma) compared with the posterior PVN (1.8-2.1 mm posterior to bregma). Jejunal administration of saline failed to affect activity of neurons located either inside or outside the PVN. When the same neurons were subsequently tested for their response to intravenous administration of 2 microg/kg of CCK-8, excitatory responses were more frequently observed than inhibitory responses, but both types of responses were observed regardless of whether neurons were located inside or outside the PVN. In addition, there was no strong correlation between the magnitude of the neuronal response evoked by jejunal administration of linoleic acid compared with intravenous CCK-8. These data suggest that neurons located in the anterior PVN may play a role in the mediation of suppression of food intake produced by intestinal administration of lipids.     

Differences in endogenous pyrogen fevers induced by iv and icv routes in rabbits

We have compared the characteristics of fevers produced by endogenous pyrogen administered by the intravenous (iv) and by the intracerebroventricular (icv) routes in conscious rabbits. Fevers induced by the intracerebroventricular route have a longer latency to onset, a less steep rise in body temperature, and a longer time to peak elevation in body temperature than do fevers induced by the intravenous route. Furthermore, a dose of indomethacin (2 mg/kg) administered intravenously, which is effective in markedly attenuating fevers produced by the intravenous route, was completely without effect on fevers induced by the intracerebroventricular route. On the other hand, when indomethacin (500 micrograms) was infused intracerebroventricularly, it markedly reduced fevers induced by the subsequent injection of endogenous pyrogen into the contralateral cerebral ventricle, but such pretreatment had little effect on fevers elicited by intravenous injections of endogenous pyrogen. It is concluded that the sites of action of endogenous pyrogen in response to intravenous injections of pyrogen are different from those responding to intracerebroventricular injections of pyrogen and that this is manifest in several distinct differences in the characteristics of the two fevers. These results indicate that the intracerebroventricular model of fever production is not appropriate for the study of the normal pathogenesis of fever.     

Neuroendocrine mechanisms of participation of the raphe nuclei in the development of hypertensive reactions in emotional stress

The experiments on cats and rabbits have studied electroencephalographic, endocrine and blood pressure responses to stress (5-hour immobilization with electrical foot shock) before and after coagulation of the midbrain nuclei raphe. Blood pressure and adrenal responses in advanced (4-hour) stress were elevated in intact animals, the responses attenuating after coagulation of the nuclei raphe. Background bioelectrical activity of the midbrain reticular formation and hypothalamus was found to be activated in the operated animals. Stress was followed by the reduction in bioelectrical changes of the above subcortical structures with the parallel development of "burst" activity in the dorsal hippocamp.     

Reduction of the hyperthermic effect of prostaglandin E2 by cholinomimetics, monoamines and calcium ions]

It was shown in experiments on unanesthetized rats with prostaglandin E2 (PGE2) hyperthermia, not preventable by aspirin that intraventricular (into the lateral ventricle) injections of arecoline, noradrenaline, 5-hydroxytryptamine (5-HT), histamine, and calcium ions and intraperitoneal eserine injection were capable of decreasing body temperature. PGE2 hyperthermia was not prevented by aspirin, but it was reduced by eserine. After the administration of arecoline and nicotine into the third ventricle of unanesthetized rabbits with PGE2 hyperthermia body temperature decreased as well. The effect of arecoline and 5-HT was reproducible in the same animals. The data are suggestive of the existence in the heat loss centre of mechanisms including cholinergic neurons whose activity was not completely suppressed by PGE2.     

Unit activity of the posterior hypothalamus during brain and skin temperature changes in unanesthetized rabbits

Changes in the firing rate of posterior hypothalmic neurons in response to local elevation of the brain temperature by 0.6–1.5°C and to a rise and fall (separately and simultaneously) of the skin temperature by 3–5°C were investigated in unanesthetized rabbits. Neurons responding selectively to changes in brain temperature and skin temperature and neurons responding to both temperature stimuli were found in the posterior hypothalamus. During combined stimulation the unit activity was changed much more than in response stimulus. It is concluded that the region of the posterior hypothalamus participates in the integration of impulses from central and peripheral temperature receptors.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 5, pp. 490–496, September–October, 1973.     

Effects of hypotension and fluid depletion on central angiotensin-induced thirst and salt appetite

We examined the effects of hypotension and fluid depletion on water and sodium ingestion in rats in response to intracerebroventricular infusions of ANG II. Hypotension was produced by intravenous infusion of the vasodilator drug minoxidil (25 microg x kg(-1) x min(-1)) concurrently with the angiotensin-converting enzyme inhibitor captopril (0.33 mg/min) to prevent endogenous ANG II formation. Hypotension increased water intake in response to intracerebroventricular ANG II (30 ng/h) but not intake of 0.3 M NaCl solution and caused significant urinary retention of water and sodium. Acute fluid depletion was produced by subcutaneous injections of furosemide (10 mg/kg body wt) either alone or with captopril (100 mg/kg body wt sc) before intracerebroventricular ANG II (15 or 30 ng/h) administration. Fluid depletion increased water intake in response to the highest dose of intracerebroventricular ANG II but did not affect saline intake. In the presence of captopril, fluid depletion increased intakes of both water and saline in response to both doses of intracerebroventricular ANG II. Because captopril administration causes hypotension in fluid-depleted animals, the results of the two experiments suggest that hypotension in fluid-replete animals preferentially increases water intake in response to intracerebroventricular ANG II and in fluid-depleted animals increases both salt and water intake in response to intracerebroventricular ANG II.     

Site-specific modulation of LPS-induced fever and interleukin-1 beta expression in rats by interleukin-10

Bacterial lipopolysaccharide (LPS) induces fever that is mediated by pyrogenic cytokines such as interleukin (IL)-1 beta. We hypothesized that the anti-inflammatory cytokine IL-10 modulates the febrile response to LPS by suppressing the production of pyrogenic cytokines. In rats, intravenous but not intracerebroventricular infusion of IL-10 was found to attenuate fever induced by peripheral administration of LPS (10 microg/kg iv). IL-10 also suppressed LPS-induced IL-1 beta production in peripheral tissues and in the brain stem. In contrast, central administration of IL-10 attenuated the febrile response to central LPS (60 ng/rat icv) and decreased IL-1 beta production in the hypothalamus and brain stem but not in peripheral tissues and plasma. Furthermore, intravenous LPS upregulated expression of IL-10 receptor (IL-10R1) mRNA in the liver, whereas intracerebroventricular LPS enhanced IL-10R1 mRNA in the hypothalamus. We conclude that IL-10 modulates the febrile response by acting in the periphery or in the brain dependent on the primary site of inflammation and that its mechanism of action most likely involves inhibition of local IL-1 beta production.     

Effect of beta-endorphin on the thermal excitability of preoptic neurons in the unanesthetized rabbit

The opioid peptide, beta-endorphin (beta-E), will promote changes in body temperature when injected into the brain. It is possible that beta-E alters body temperature by affecting the activity of thermoregulatory neurons in the preoptic anterior hypothalamus (POAH). Single unit activity in the POAH was recorded in unanesthetized rabbits while radiant heat was applied to the dorsal skin. Beta-E was then microinjected into the POAH, and the peripheral heating was repeated. Seventy-seven percent of the POAH neurons were responsive to skin heating. Beta-E and equal excitatory and inhibitory effects on warm-excited and warm-inhibited neurons. Four of six warm-excited neurons were converted to warm-inhibited or unresponsive following beta-E injection. Six out of ten warm-inhibited neurons were converted to warm-excited or unresponsive by beta-E. Beta-E-induced shifts in thermal excitability of POAH neurons may be responsible for the ability of POAH injections of beta-E to elevate body temperature in the rabbit.     

A study of the variability in the febrile responses of rabbits to endogenous pyrogen

The range of body temperature increases elicited by a standard dose of endogenous pyrogen (0.5 ml/kg iv) was examined in a population of 26 male New Zealand White rabbits. Although the mean maximum increase in rectal temperature was 0.88 +/- 0.06 degree C (SE), individual responses varied from 0.4 degree to 1.5 degree C. Three representative animals that responded to the standard dose of pyrogen with small, intermediate, and large febrile responses were selected and challenged with the same dose of pyrogen on eight separate occasions, and the variability of these responses was examined. There was little variability within the characteristic responses of any particular animal to the repeated challenges. The variability of the febrile responses elicited by both intravenous and intracerebroventricular administration of the same pyrogen was examined and compared using another group of 11 rabbits. The variability in response to the intravenous route was similar to that found in the larger population, whereas the variation in response to the intracerebroventricular route was smaller, and all 11 animals had fevers that were greater than 1 degrees C. It is concluded that the variability of the febrile responses of rabbits to intravenous pyrogen was due to differences between individual sensitivities of animals to the intravenously administered pyrogen. This difference in sensitivity may be due to a difference in the amount of pyrogen that reaches the putative receptor sites, or to a difference in the density or effectiveness of receptor sites in translating the pyrogenic stimulus into a fever response.     

Glial cell line-derived neurotrophic factor promotes sleep in rats and rabbits

Various growth factors (e.g., growth hormone-releasing hormone, acidic fibroblast growth factor, nerve growth factor, brain-derived neurotrophic factor, and interleukin-1) are implicated in sleep regulation. It is hypothesized that neuronal activity enhances the production of such growth factors, and they in turn form part of the sleep regulatory mechanism. Glial cell line-derived neurotrophic factor (GDNF) promotes development, differentiation, maintenance, and regeneration of neurons, and its production is induced by well-characterized sleep regulatory substances such as interleukin-1 and tumor necrosis factor. Therefore, we investigated whether GDNF would promote sleep. Twenty-six male Sprague-Dawley rats and 30 male New Zealand White rabbits were surgically implanted with electroencephalogram (EEG) and electromyogram (EMG; rats only) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly with pyrogen-free saline and on a separate day with one of the following doses of GDNF: 5, 50, and 500 ng in rabbits and 50 and 500 ng in rats. The EEG, brain temperature, EMG (in rats), and motor activity (in rabbits) were recorded for 23 h after the intracerebroventricular injection. GDNF (500-ng dose) increased the time spent in nonrapid eye movement sleep in both rats and rabbits. Rapid eye movement sleep was not affected by the lower doses of GDNF but was inhibited in rabbits after the high dose. EEG slow-wave activity was not affected by GDNF. The current results provide further evidence that various growth factors are involved in sleep regulation.     

Projections of the posterior area of the hypothalamus to its medial,anterior, and lateral areas

The effect of stimulation of the lateral and medial supramammillary areas of the posterior hypothalamus on spontaneous single unit activity in the anterior, lateral, medial dorsal, and medial ventral areas of the hypothalamus was investigated in acute experiments on rabbits. Single stimulation of the medial area of the posterior hypothalamus evoked responses of 44% of neurons, whereas stimulation of the lateral area did so in only 35% of all neurons recorded. Repetitive stimulation led to an increase in the number of responding neurons (to 57% during stimulation of the lateral and 74% during stimulation of the medial supramammillary area). In response to repetitive stimulation of the medial supramammillary area, activating influences became predominant in all areas, whereas in response to stimulation of the lateral area, they became predominant in the medial, ventral, and lateral areas. The results are assessed from the standpoint of the role of the posterior hypothalamus in the regulation of adenohypophyseal functions.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 9, No. 4, pp. 377–381, July–August, 1977.     

Changes in the bioelectrical activity and temperature of paired brain formations in the rabbit in a single ethanol administration

In chronic experiments on rabbits, in initial period of single action of ethanol, reduction was observed of the dominating frequency of the theta-rhythm and synchroneity of summated bioelectrical activity of homotopic zones and suppression of EEG manifestation but preservation of parameters of the interhemispheric zeta-wave and of temperature asymmetry in the dorsal hippocampus in response to electro-cutaneous stimulation. Late period of ethanol action was characterized by lowering of the amplitude of superslow activity, its inversion in symmetrical areas of the visual neocortex and instability of other parameters.