Action of an enkephalinase blocker on the effect of acupuncture in acupuncture sensitive and resistant rabbits]

In unanaesthetized acupuncture-sensitive rabbit d-phenylalanine injection didn't change the EP in response to tooth pulp electrostimulation, but prolonged the analgetic effect of auriculo-acupuncture stimulation 15 Hz expressed by decreasing of the amplitude of N1P2 component EP. In acupuncture-resistant rabbit d-phenylalanine injection induced analgetic effect which was enhanced and prolonged by auriculo-acupuncture stimulation. It's suggested that the recovery of pain sensibility after acupuncture analgesia is determined by enkephalinase's mechanism activation which is activated permanently in acupuncture-resistant rabbits.     

Role of the vagus nerve in mechanisms of the modulation of afferent duodenal effects]

The electrostimulation of vagal nerves, the effect of naloxone and atropine on duodenal afferentation by registering evoked potential (EP) at cortex on direct electrostimulation of duodenum have been studied in acute experiments on cats. It has been established that the stimulation of afferent portion of vagal nerves causes the effect of deprivation of EP, whereas the stimulation with certain intensity of efferent portion of vagal nerves intensifies the duodenal afferentation. The effect of afferentation easeness (relief) has been blocked by the application of naloxone 10-20 microgram on duodenal bulbus, but not on it's i. v. injection and without effect on local application of atropine. It is concluded that the role of vagal nerves on the modulation of duodenal nociception is due to the activation of opiate terminals of the efferent vagal nerve portions.     

Angiotensin II in the organization of rat feeding behavior

Intraventricular injection of angiotensin-II (100 ng) increased the latency period and decreased the amount of food intake in the hungry rats. Preliminary administration of saralasin (100 ng) blocked the inhibitory effect of angiotensin-II on food consumption. In contrast to the above mentioned intraperitoneal injection of angiotensin-II (10 ng/kg) 10 min before food and water admission results in the tendency to increase the food intake. And the same application of angiotensin-II 60 min before food and water admission increased by 49% of food intake in hungry rats. Saralasin (50 ng/kg) given prior to the angiotensin-II administration blocked the angiotensin-II effects. Moreover a significant decrease in the food intake was found after intraperitoneal injection of saralasin only. No significant changes in the drinking behavior in response to the intraventricular and intraperitoneal drugs administration were registered.     

高频电刺激股神经减小大鼠心肌缺血-再灌注后的梗塞范围

通过氨基甲酸乙酯麻醉大鼠观察股神经电刺激对缺血- 再灌注心肌的影响,旨在证实外周神经刺激对心肌有无保护效应,并明确其可能的作用机制。心肌缺血区和梗塞区分别用伊文思蓝和氯化硝基四氮唑蓝染色确定,心肌梗塞范围定义为心肌梗塞区重量占心肌缺血区重量的百分比。所得结果如下:(1)在心肌缺血30 min 和再灌注120 min 过程中,梗塞心肌占缺血心肌的(54.96±0.82)%。 高频电刺激(10 V,100 Hz,1ms)股神经5 min 可使心肌梗塞范围减少到(36.94±1.34)% (P<0.01), 表明 (2)高频电刺激股神经对缺血-再灌注心肌有保护作用。然而,低频电刺激(10 V, 10 Hz, 1 ms)股神经对缺血-再灌注心肌梗塞范围无影响。 预先应用非选择性阿片肽受体阻断剂纳洛酮(5 mg/kg, i.v.)或非选择性KATP 通道阻断剂格列苯脲(5 mg/kg, i.v.)均能完全 (3)取消高频电刺激股神经对缺血-再灌注心肌的保护作用。以上结果提示,高频外周神经刺激可以减小缺血- 再灌注心肌的梗塞范围,其可能的作用机制是: 高频电刺激股神经时中枢神经系统内释放的内源性阿片肽和由此激活的心肌KATP通道的开放介导了这种保护作用。     

Noncholinergic Transmitter(s) Maintains Secretion of Catecholamines from Rat Adrenal Medulla for Several Hours of Continuous Stimulation of Splanchnic Neurons

The effect of continuous stimulation of splanchnic nerves at 1, 3, and 10 Hz on the secretion of catecholamines from the isolated rat adrenal gland was examined. Secretion evoked at 10 Hz declined over 60% in 1 h, and by the end of 4 h the secretion was only 10% of the initial value. The secretion evoked at 3 Hz was unchanged in the first hour, but showed a gradual decline in subsequent hours. In contrast, secretion evoked at 1 Hz was well maintained for several hours. Even after 6 h of continuous stimulation, the decline was only about 35%. Atropine plus hexamethonium reduced the secretion evoked at 10 Hz by over 80%, but that evoked at 1 Hz was reduced by about 35%; addition of naloxone reduced it to 75%. When the secretion declined to very low levels after continuous stimulation at 10 Hz for 100 min, a change in frequency to 3 Hz or 1 Hz caused a sharp rebound in the secretory response. Returning the frequency back to 10 Hz led to a sharp drop in the secretion, whereas reducing the frequency to 1 or 3 Hz once again increased the secretion. The rebound in the secretory response after switchover of frequencies was observed in the presence of atropine plus hexamethonium, but was abolished by naloxone. Extensive stimulations, which caused large amounts of catecholamine secretions at each frequency, were not associated with any loss in tissue catecholamine contents. The major conclusion is that secretion of catecholamines is maintained uninterrupted for several hours when splanchnic nerves are stimulated at low frequency.(ABSTRACT TRUNCATED AT 250 WORDS)     

脊髓中P物质参与电针镇痛的研究

本研究发现,低频（２Ｈｚ）电针刺激时大鼠脊髓中Ｐ物质免疫活性（ＳＰ－ｉｒ）含量减少,中频（１５Ｈｚ）、高频（１００Ｈｚ）和变频（２／１５Ｈｚ）刺激时ＳＰ－ｉｒ含量增多。脊髓蛛网膜下腔（ｉ．ｔ．）注射非肽类ＳＰ（ＮＫＩ）受体拮抗剂ＣＰ９６３４５和ＲＰ６７５８０均能阻断中频、高频和变频的电针镇痛。ｉ．ｔ．注射阿片拮抗剂纳洛酮阻断低频和中频刺激时ＳＰ－ｉｒ含量的变化。结果提示,脊髓ＳＰ－ｉｒ在低频时释放     

Effects of auricular electrostimulation and naloxone on nociceptive sensitivity in rabbits

Auriculo-acupuncture electrostimulation (AES) (15 H2) decreased the amplitude of somatosensory evoked potential (EP) in response to tooth pulp electrostimulation in 64% of acupuncture-sensitive unanesthetized rabbits and didn't induce the changes of EP in 36% of animals (acupuncture-resistant rabbits). The systemic naloxone (0.2 mg/kg) injection reversed the AES analgetic effect and induced the hyperalgesic one in acupuncture-sensitive rabbits but induced the analgetic effect in acupuncture-resistant animals. It has been suggested that the differences of individual characteristics of endogenous opioid system determined different naloxone action in acupuncture-sensitive and acupuncture-resistant rabbits.     

Augmented analgesic effects of L-tryptophan combined with low current transcranial electrostimulation

The analgesic effects of low current transcranial electrostimulation are both naloxone and pCPA-reversible, suggesting that they may be mediated in part by endogenous opioid and serotonergic activity. The present experiments indicate that pretreatment with the serotonin precursor L-tryptophan results in an increased analgesic effect of electrostimulation as measured by the 50 degrees C wet tail flick test in the rat. Rats receiving both L-tryptophan and electrostimulation displayed significantly more analgesia than rats receiving electrostimulation and injection vehicle alone, rats receiving drug and sham stimulation or rats receiving vehicle and sham stimulation.     

Role of endogenous opiates and extracellular K+ accumulation in the inhibition of frog spinal reflexes by electrical skin stimulation

Electrical skin stimulation of the hind limb (10-100 Hz, 30 s-5 min) at the intensity which leads only to the excitation of low threshold afferents depressed (for 1-30 min) the flexor reflex evoked in spinal frogs by nociceptive stimuli. The inhibition, which lasted for longer than 5 min was blocked by naloxone. Short-term poststimulation effects were associated with an increase of extracellular K+ concentration (delta [K]e) and were not blocked by naloxone. Enkephalins or morphine applied to the spinal cord surface increased the threshold for flexor reflexes while naloxone decrease their threshold. The stimulation was followed by short-term hyperpolarization of primary afferents (PAH; 1-5 min) and by depression of dorsal root potentials (DPRs) which had a similar time course to the delta [K]e, and were not blocked by naloxone. This period was frequently followed by longlasting PAH and enhancement of DRPs (5-30 min), which were abolished by naloxone. Superfusion of the isolated spinal cord with opioids produced PAH and enhanced DRPs evoked by nociceptive stimuli, while naloxone or increase of [K] in Ringer solution depolarized primary afferents and depressed DRPs. It is suggested that the antinociceptive effects of electrical stimulation of low threshold cutaneous afferents in spinal frogs involves at least two mechanisms. The short-term effect may result from delta [K]e, especially at high stimulus strength and is equally effective against noxious and non-noxious stimuli. The longlasting effects selectively affecting nociceptive transmission appear to be produced by endogenous opioids.     

Opioids and hibernation. I. Effects of naloxone on bear HIT'S depression of guinea pig ileum contractility and on induction of summer hibernation in the ground squirrel

Summer hibernation in ground squirrels (Citellus tridecemlineatus) can be induced by intravenous injection of hibernation-induction trigger (HIT) from winter bear plasma or its albumin fraction. In this study, we show that bear HIT depresses electrically-induced contraction of the guinea pig ileum myenteric plexus-longitudinal muscle preparation, and that naloxone, at 100, 1,000, or even 4,000 nM, fails to reverse that effect. In a simultaneous study, four sets of ground squirrels were implanted with osmotic minipumps which delivered solutions at a controlled and continuous rate. Two of the groups had pumps delivering naloxone at 1 mg/kg body weight per hour. The other two groups had saline-filled pumps (controls). One set of squirrels from each of the saline- and naloxone-filled pump groups were then injected intravenously with winter bear plasma. The remaining two groups of squirrels were injected with winter bear albumin fraction. Hibernation frequency was determined by measurements of core temperature (from surgically-implanted radio capsules), respiratory rate, and bouts of activity. Squirrels with saline-filled pumps hibernated four times more frequently than the naloxone groups. To confirm these findings, three squirrels from each naloxone group were reinjected with bear HIT after removal of the pumps. These six squirrels then hibernated over four times their previous frequency. Results suggest that bear HIT is not itself an opioid (since naloxone did not reverse bear HIT's depression of electrically-induced contraction of guinea pig ileum). The fact that bear HIT's effect of inducing summer hibernation in ground squirrels is effectively blocked in vivo by naloxone leads to the speculation that HIT may be either a precursor of endogenous opioids or a potent releaser of them, which, in turn, induce hibernation.     

Octreotide-induced drinking, vasopressin, and pressure responses: role of central angiotensin and ACh

The involvement of central angiotensinergic and cholinergic mechanisms in the effects of the intracerebroventricularly injected somatostatin analog octreotide (Oct) on drinking, blood pressure, and vasopressin secretion in the rat was investigated. Intracerebroventricular Oct elicited prompt drinking lasting for 10 min. Water consumption depended on the dose of Oct (0.01, 0.1, and 0. 4 microgram). The drinking response to Oct was inhibited by pretreatments with the intracerebroventricularly injected angiotensin-converting enzyme inhibitor captopril, the AT(1)/AT(2) angiotensin receptor antagonist saralasin, the selective AT(1) receptor antagonist losartan, or the muscarinic cholinergic receptor antagonist atropine. The dipsogenic effect of Oct was not altered by prior subcutaneous injection of naloxone. Oct stimulated vasopressin secretion and enhanced blood pressure. These responses were also blocked by pretreatments with captopril or atropine. Previous reports indicate that the central angiotensinergic and cholinergic mechanisms stimulate drinking and vasopressin secretion independently. We suggest that somatostatin acting on sst2 or sst5 receptors modulates central angiotensinergic and cholinergic mechanisms involved in the regulation of fluid balance.     

Intracerebroventricular injection of mu- and delta-opiate receptor antagonists block 60 Hz magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat

In previous research, we have found that acute exposure to a 60 Hz magnetic field decreased cholinergic activity in the frontal cortex and hippocampus of the rat as measured by sodium-dependent high-affinity choline uptake activity. We concluded that the effect was mediated by endogenous opioids inside the brain because it could be blocked by pretreatment of rats before magnetic field exposure with the opiate antagonist naltrexone, but not by the peripheral antagonist naloxone methiodide. In the present study, the involvement of opiate receptor subtypes was investigated. Rats were pretreated by intracerebroventricular injection of the mu-opiate receptor antagonist, β-funaltrexamine, or the delta-opiate receptor antagonist, naltrindole, before exposure to a 60 Hz magnetic field (2 mT, 1 hour). It was found that the effects of magnetic field on high-affinity choline uptake in the frontal cortex and hippocampus were blocked by the drug treatments. These data indicate that both mu- and delta-opiate receptors in the brain are involved in the magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat. Bioelectromagnetics 19:432–437, 1998. © 1998 Wiley-Liss, Inc.     

强啡肽和心钠素可能参与可乐定的降压利尿作用

静脉注射可乐定引起大鼠血压降低和心率减慢。此效应可被α受体阻断剂酚妥拉明所对抗。预先腹腔注射大剂量阿片受体阻断剂纳洛酮或静脉注射强啡肽抗体可以部分阻断可乐定的降压效应。静脉注射可乐定可以引起大鼠尿量显著增加,该效应也可被大剂量的纳洛酮所阻断。静脉注射可乐定引起明显的心钠素释放,这一作用可被α受体阻断剂所完全对抗,亦可被阿片受体阻断剂所部分阻断。以上结果说明强啡肽与心钠素可能参与可乐定的降压利尿作用。     

Factors affecting angiotensin II-induced hypothermia in rats

Systemic administration of angiotensin II (AII) to the rat has previously been shown to induce a dose-dependent, hypothermic response manifested by a fall in colonic temperature (CT), a decrease in heat production and an increase in tail skin temperature (TST). The factors mediating AII-induced hypothermia and their site of action were the subjects of the present investigation. To this end, intracerebroventricular administration of 1 microgram of AII induced a 0.4 degrees C reduction in CT and a 2.4 degrees C increase in TST. In contrast, SC administration of 200 micrograms angiotensin III/kg induced a slight increase in CT but had no affect on TST. Pretreatment with the AII-receptor antagonist, saralasin, at either 1 or 10 micrograms/kg, SC did not affect either the fall in CT or the increase in TST induced by administration of 200 micrograms AII/kg, SC. However, the administration of 100 micrograms saralasin/kg, SC attenuated both the fall in CT and the increase in TST induced by either 100 or 200 micrograms AII/kg. Since both the presynaptic alpha adrenoceptor agonist, clonidine, and the opioid antagonist, naloxone, modulate the pressor and dipsogenic responses to AII, their effects on AII-induced hypothermia were tested. Both clonidine (25 micrograms/kg, SC) and naloxone (1 mg/kg, IP) enhanced the fall in CT. Clonidine lengthened the duration of the increase in TST while naloxone had no effect. Pretreatment with the presynaptic adrenoceptor antagonist, yohimbine (300 micrograms/kg, SC), did not alter the hypothermic response to administration of AII. To determine whether vasodilation of the tail of the rat was mediated by AII-induced prostaglandin release, indomethacin (4 and 6 mg/kg) was administered.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional studies of nerve projections in the canine intestine

An in vivo model has been developed to study nerve connections in the canine intestine, using spread of field stimulated contractions recorded proximally and distally with strain gauges and local intra-arterial injections of drugs. Excitation spread orally for several centimetres, more effectively at lower frequencies of field stimulation. This excitation was blocked by local hexamethonium or by a combination of atropine and naloxone (each of which reduced the contractions). Distal excitation occurred after a longer delay than oral excitation; during the delay there was frequently an initial relaxation response. Distal excitation was greater at higher frequencies of field stimulation, but like oral excitation it was blocked by hexamethonium or by a combination of atropine and naloxone. Distal relaxation responses were unaffected by atropine or naloxone, but were abolished by hexamethonium. "Off" contractions, those that followed cessation of field stimulation, occurred at higher frequencies of field stimulation proximally and distally near the site of field stimulation and were blocked by atropine but not by naloxone or hexamethonium. The effects of all agents given locally extended beyond the sites of injection. These results suggest that a chain of cholinergic nerves with nicotinic synapses transmit excitation orally and distally to circular muscle; these effects seem to be facilitated proximally and distally by opioid nerves and to be inhibited initially distally by a noncholinergic mechanism. Explanations of these findings are proposed.     

刺激大脑皮层联合区对C类纤维传入诱发皮层电反应的影响

电刺激猫大脑皮层前外侧回联合区(ALA)能使隐神经 C 类纤维传入引起的体感皮层(S(?)区)诱发电位(C-CEP)的幅值明显变小,并有后作用,表明 ALA 对 C-CEP 有抑制作用;切断ALA 与 SI 区之间的皮层内纤维联系后,ALA 对 C-CEP 的抑制作用明显减弱,抑制时程缩短;侧脑室微量注射阿片受体拮抗剂纳洛酮后,电刺激 ALA 对 C-CEP 的抑制作用明显减弱,表明 ALA 对 C-CEP 的抑制作用的作用途径之—可能是通过 ALA 与 SI 区之间的皮层内神经径路;可能与内源性阿片样物质的释放有关。提示大脑皮层联合区可能对体感皮层 C-CEP 有调制作用。     

Alleviation of narcotic withdrawal syndrome by conditional stimuli.

We systematically paired auditory, olfactory, and social stimuli with each injection of morphine in rats. We found that, when morphine was kept constant at a low dose, the external stimuli acquired the property of a conditional stimulus (CS) to cause hyperthermia which was antagonized by naloxone. In rats in which morphine doses were regularly increased to cause morphine dependence, the CS presented during withdrawal, caused reduction in withdrawal signs (wet shakes, hypothermia, aggression) and produced hyperglycemia as well as elevation of striatal homovanillic acid. CS-induced alleviation of withdrawal hypothermia was blocked by mecamylamine, phenoxybenzamine, haloperidol, benztropine or naloxone but not by cyproheptadine or propranolol.     

Hippocampal involvement in the pharmacologic induction of withdrawal-like behaviors

Kainic acid is an analog of glutamate. The CA3-4 field of the hippocampus is extremely sensitive to its toxic properties. Intracerebroventricular injection of of nontoxic doses of kainic acid in rats produces behaviors similar to morphine withdrawal. Lesion of CA3-4 abolishes this response to kainic acid. Destruction of CA3-4 blocks the ability of Met-enkephalin, ketocyclazocine, and 5-hydroxytryptophan, but not sodium valproate or ice water to induce withdrawal-like behaviors. The actions of kainic acid, endorphins, and ketocyclazocine are blocked by naloxone and enhanced by opiate agonists. Sodium valproate, ice water, and withdrawal itself are released by naloxone and blocked by opiate agonists. Similar discriminations by CA3-4 lesions and challenge by naloxone and morphine may indicate that two neural circuits exist through which withdrawal-like behaviors are evoked. The hippocampal circuit is not directly involved in dependence, but may modulate withdrawal. Withdrawal-like behaviors are observed in rats in situations where behavior is blocked. These withdrawal-like behaviors are reminiscent of verbal reports of anxiety. In particular, wet-dog shakes in these situations may be analogous to shuddering. In humans, monosodium glutamate intolerance is associated with shuddering.     

Effect of neuromediating and neuroblockading hormones on the RNA synthesis in the rat liver nucleus

It was shown that rRNA and HnRNA synthesis in rat liver nuclei does not change-within 30 min after intraperitoneal injection of acetylcholine (0.005 mg per 100 g of body weight) but decreases after injection of norepinephrine and epinephrine (0.05 mg per 100 g of body weight). The synthesis of rRNA (but not of HnRNA) increases after injection of hydrocortisone (2,5 mg per 100 g of body weight). The synthesis of HnRNA (but not of rRNA) increases after injection of ACTH1-24 (3 ME per 100 g of body weight) and oxytocin (1 ME per 100 g of body weight). The synthesis of rRNA decreases after injection of propranolol and atropine (0.5 mg per 100 g of body weight). At the same time, the synthesis of HnRNA does not change thereby. The inhibitory effect of propranolol and atropine was corrected by electrostimulation of hypothalamus. The content of cAMP and Ca2+ and the phosphorylation degree of nuclear proteins are increased after stimulation of hypothalamus. The phosphorylation of nuclear proteins is increased by 10(-8)-10(-6) M cAMP. The synthesis of RNA in liver nuclei is increased by 10(-6) M cAMP only after addition of cytosol. In this case the activity of RNA-polymerase II increases in a greater degree than that of RNA-polymerase I + III. It is assumed that the regulatory mechanisms of rRNA and HnRNA synthesis are different. The role of hypothalamus electrostimulation, neurotransmitters, hormones, and cAMP in the mechanisms of RNA synthesis in rat liver nuclei is discussed.     

Effect of angiotensin II and saralasin on motor activity and the passive avoidance behavior of rats

One nmole of angiotensin II (ANG II) or saralasin, given intracerebroventricularly, failed to alter the motor activity of rats in open field. A combined injection of both peptides caused a significant decrease of the number of crossings and rearings. In the electromagnetic motimeter horizontal activity of animals was changed by neither of the peptides while the vertical activity was increased by ANG II. Again, a combined injection of saralasin and ANG II inhibited both horizontal and vertical activity. Stereotypies evoked by both apomorphine (2 mg/kg) and amphetamine (6.5 mg/kg), given intraperitoneally, were markedly intensified by ANG II and saralasin. A five-fold increase of the re-entry latencies in the passive avoidance situation was observed after pre-test administration of ANG II or saralasin but not the two in combination. These results suggest that ANG II and saralasin may improve processes related to learning and memory through an unspecific mechanism involving central dopamine systems.