中缝背核5-羟色胺能神经元在睡眠调节中的作用研究

目的：研究中缝背核(DRN)5-羟色胺(5-HT)能神经元在睡眠中的调节作用。方法：运用脑立体定位、核团微量注射和多导睡眠描记(PSG),观察DRN 5-HT能神经元对大鼠睡眠的影响。结果：DRN微量注射谷氨酸钠(L-Glu),大鼠睡眠减少,特别是深慢波睡眠(SWS2)明显减少,觉醒(W)增加;DRN微量注射海人酸(KA)和对氯苯丙氨酸(PCPA),大鼠SWS2和异相睡眠(PS)增加,W减少。结论：DRN 5-HT能神经元参与睡眠的调节,兴奋DRN 5-HT能神经元睡眠时间减少,抑制DRN 5-HT能神经元则具有促进睡眠的作用。     

大鼠海马CA1区GABA能神经元在睡眠调节中的作用

采用脑立体定位技术确定Sprague-Dawley大鼠(Rattus norregicus)双侧海马CA1区插管位置并进行核团埋管,同时安装脑电和肌电电极,用于记录大鼠皮层脑电活动和肌电活动。运用睡眠描记技术观察海马CA1区微量注射药物后对大鼠睡眠-觉醒周期的影响。发现海马内微量注射0.75μg、1.0μg的γ-氨基丁酸(GABA)后觉醒时间增加,分别为(120.7±13.3)min和(124.6±19.2)min(P0.05),睡眠时间减少,分别为(119.4±13.3)min与(115.4±19.2)min(P0.05),其中,深慢波睡眠时间(SWS2)分别减少53.3%(t=2.451,P0.05)和63.5%(t=3.367,P0.01);而微量注射1.0μgGABAA受体阻断剂荷包牡丹碱(Bic)后,睡眠时间增加(165.5±20.8)min(P0.01),觉醒时间减少(74.5±20.8)min(P0.01),其中,SWS2时间增加79.6%(t=2.600,P0.05),并可对抗GABA的促醒效应;微量注射GABAB受体激动剂氯苯氨基丁酸(Bac)对睡眠-觉醒周期无直接影响,亦不能阻断GABA的促醒效应。结果提示,GABA在海马参与大鼠睡眠-觉醒周期的调节且具有促觉醒作用,GABA对睡眠的影响主要是通过改变深慢波睡眠成分实现的,GABAA受体参与介导了这一过程。     

吗啡对大鼠海马神经元突触传递的作用及机制探讨

目的 :从离子通道角度研究吗啡对中枢神经系统兴奋性及抑制性突触传递的作用并探讨其机制。方法 :　原代培养新生Wistar大鼠的海马神经元。采用膜片钳技术研究吗啡对其兴奋性及抑制性突触后电流及谷氨酸诱发电流的影响。结果 :①吗啡可明显增强海马神经元兴奋性突触传递 ,加吗啡后自发兴奋性突触后电流 (sEPSC)的发放频率增加了 ( 2 0 7.8± 2 0 .9) %。此作用可被阿片受体阻断剂纳洛酮阻断 (P <0 .0 1) ;②吗啡对微小兴奋性突触后电流 (mEPSC)的发放频率及谷氨酸诱发电流的幅度没有明显影响 (P >0 .0 5 ) ;③吗啡可明显抑制神经元自发抑制性突触后电流 (sIPSC) ,纳洛酮可拮抗吗啡作用 (n =13 ,P <0 .0 1)。结论 :实验结果提示吗啡对海马神经元的兴奋作用不是由于吗啡直接作用于兴奋性氨基酸—谷氨酸突触传递过程 ,而是可能由于抑制了抑制性中间神经元 ,间接产生的兴奋作用。     

微清蛋白中间神经元在氯胺酮抗抑郁中的作用

目的:观察微清蛋白(PV)中间神经元在氯胺酮抗抑郁中的作用。方法:32只Wistar雄性大鼠随机均分为4组(n=8),包括生理盐水组(S组)、氯胺酮组(K组)、夹竹桃麻素预处理+生理盐水组(AS组)、夹竹桃麻素预处理+氯胺酮组(AK组)。夹竹桃麻素预处理组将药物溶于大鼠饮水中,共喂养1周,于第8 d制备模型。大鼠强迫游泳15 min制备急性应激抑郁模型,24 h后给大鼠分别腹腔注射1 mL生理盐水或氯胺酮10 mg/kg,给药后0.5 h行敞箱实验记录大鼠水平运动及垂直运动得分,行强迫游泳6 min记录后5 min内不动时间。行为学测试结束后,取大鼠前额皮层,Western印迹检测PV中间神经元中PV及谷氨酸脱羧酶67(GAD67)的表达。结果:与S组相比,K组大鼠强迫游泳不动时间减少,PV及GAD67的表达下降(P0.05),AS组则无显著变化(P0.05);与K组相比,AK组大鼠强迫游泳不动时间增加,PV及GAD67的表达增加(P0.05)。生理盐水、氯胺酮、夹竹桃麻素均未显著影响大鼠自主活动(P0.05)。结论:氯胺酮通过下调大鼠前额皮层PV中间神经元功能发挥快速有效的抗抑郁作用。     

眶额叶区5-HT与Glu、NO在急性强迫游泳应激抑郁症模型中的关系

目的：探讨眶额叶区5-羟色胺（5-HT）与谷氨酸（Glu）、一氧化氮（N0）在急性强迫游泳应激抑郁症模型中的相互作用。方法：雄性SD大鼠随机分为对照组及各种药物注射组,强迫游泳制造大鼠应激性抑郁模型,眶额叶区微量注射各组药物,敞箱实验及游泳测试观察大鼠的抑郁样行为表现。结果：①与对照组比,注射Glu使大鼠强迫游泳不动时间显著增加;注射NMDA受体拮抗剂（MK-801）使大鼠强迫游泳不动时间减少;与Glu组比,MK-801预注射后Glu注射使大鼠强迫游泳不动时间减少;②与5-HT组比,MK-801预注射后5-HT注射使大鼠强迫游泳不动时间增加;③与对照组比,注射L-精氨酸（L-Ars）使大鼠强迫游泳不动时间显著增加;注射NOS抑制剂（L-NAME）（10μg/μl）使大鼠强迫游泳不动时间减少;L-NAME（20μg／μl）注射使大鼠强迫游泳不动时间增加;L-NAME（40μg/μl）注射使大鼠强迫游泳不动时间增加;④与L-NAME（10μg/μl）组比较,5-HT1A受体拮抗剂spipemne预注射后LNAME（10μg／μl）注射使大鼠强迫游泳不动时间增加。结论：眶额叶（OFC）区Glu含量的增加能够诱发抑郁,其作用可能主要是通过NMDA受体实现的,Glu经NMDA受体引发抑郁的同时还可能通过调节突触后膜上5-HT1A受体减弱5-HT的抗抑郁作用;OFC区NO可通过调节5-HT神经元进而参与抑郁的发生。     

大鼠眶额叶GABA及其B型受体在应激性抑郁行为发生中的作用及其影响机制

为了探讨眶额叶(orbital frontal cortex,OFC)GABA及其B型受体在应激性抑郁行为发生中的作用及其影响机制,实验采用强迫游泳方法建立急性应激抑郁模型。在OFC区微量注射γ-氨基丁酸(γ-aminobutyric acid,GABA)及其B型受体阻断剂,通过开场实验、强迫游泳方式检测动物行为学表现,用免疫组织化学染色和Western blotting方法检测OFC区Kalirin表达,用高尔基染色法观察锥体细胞树突和树突棘。结果显示:强迫游泳应激引起动物抑郁样行为表现,同时,OFC区Kalirin阳性颗粒数及表达量显著减少,且锥体细胞树突棘密度下降;OFC区微量注射GABA具有抗抑郁效应,使OFC区Kalirin表达显著升高,锥体细胞树突棘密度增加;GABA-B型受体阻断剂CGP35348可以抑制GABA的这种效应。由此可见,通过强迫游泳应激诱发的抑郁样的行为变化与OFC区Kalirin表达减少和神经元树突棘密度降低有关,GABA可能通过GABA-B型受体增加OFC区Kalirin表达,以防止神经元退行性变化而产生抗抑郁作用。     

谷氨酸、NMDA 和吗啡对培养大鼠星形胶质细胞内钙振荡的影响

目的:研究谷氨酸、NMDA、吗啡对原代培养的大鼠星形胶质细胞的胞内钙信号的影响及受体作用机制.方法:利用Leica AF6000活细胞工作站,检测谷氨酸、NMDA、吗啡分别灌流前后Fura-2/AM加载的星形胶质细胞内钙信号的动态变化,进一步观 察分别阻断代谢性谷氨酸受体5 (mGluR5)、NMDA受体(NMDA receptor,NMDAR)和阿片μ受体对诱导的胞内钙振荡的影响.结果:谷氨酸、NMDA、吗啡均可明显升高胞内游离钙的浓度([Ca2+]i),而将其相应受体拮抗后,星形胶质细胞[Ca2+]i升高的现象可以被显著抑制.结论:离体培养的星形胶质细胞膜上存在mGluR5、NMDAR和阿片μ受体,这些受体的激活可以升高星影胶质细胞的[Ca2+]i,且这些受体依赖的[Ca2+]i的调控机制可能是星形胶质细胞与神经元交互作用的重要途径之一.     

强啡肽A_(1-13)对谷氨酸诱导的大鼠C6胶质瘤细胞肿胀的影响

目的和方法 :探讨脑水肿发病的细胞机制 ,采用 [3H]OMG摄取的方法测定细胞含水量 ,观察DynA对谷氨酸诱导的大鼠C6胶质瘤细胞肿胀的影响。结果 :①给予 0 .5 ,1.0 ,10 .0mmol/L的谷氨酸作用 1h均可引起细胞的含水量增加 ;②DynA可显著降低谷氨酸诱导肿胀的大鼠C6胶质瘤细胞含水量 ;③κ阿片受体拮抗剂nor BNI可阻断DynA1-13 降低谷氨酸诱导肿胀的大鼠C6胶质瘤细胞含水量的作用。结论 :谷氨酸可诱导大鼠C6胶质瘤细胞肿胀 ;DynA1-13 可通过激活κ阿片受体抑制谷氨酸诱导的大鼠C6胶质瘤细胞肿胀     

吗啡对培养海马神经元钙离子作用的机制研究

目的：研究吗啡对海马神经元[Ca^2 ]i影响的机制,为探索吗啡成瘾的神经生物学机制与可能的治疗途径。方法：荧光探针Fluo-4标记细胞内游离钙后,用激光共聚焦显微镜检测吗啡对大鼠原代培养海马神经元[Ca^2 ]i的影响。结果：吗啡急性刺激引起海马神经元[Ca^2 ]i升高,CTOP不能阻断吗啡引起的细胞内[Ca^2 ]i增加,而naltrindole能阻断吗啡引起的细胞内[Ca^2 ]i反应;Thapsigargin预处理阻断吗啡诱导的细胞内[Ca^2 ]i增加,Verapamil预处理不能完全抑制吗啡引起的细胞内[Ca^2 ]i增加;吗啡长时程作用后,海马神经元[Ca^2 ]i升高,加入纳络酮急性戒断后,不能阻断吗啡引起的细胞内[Ca^2 ]i升高,反而引起[Ca^2 ]i异常升高。结论：吗啡急性刺激引起的海马神经元内游离钙增加主要来源于δ2阿片受体介导的IP3敏感的钙库释放。     

鞘内注射M受体和GDNF反义寡脱氧核苷酸抑制吗啡戒断大鼠蓝斑c-Fos表达

应用免疫组化方法观察鞘内注射毒蕈碱型乙酰胆碱(muscarinic acetylcholine receptor,M) 受体和胶质细胞源性神经营养因子(glial cell derived neurotrophic factor,GDNF)反义寡脱氧核苷酸对吗啡戒断大鼠蓝斑(locus coeruleus,LC)区内Fos表达的影响。结果显示,鞘内注射M_2受体和GDNF反义寡脱氧核苷酸明显减少大鼠吗啡戒断症状评分值(n=6,P<0.05)。正常大鼠LC区神经元Fos基础表达较低,吗啡依赖大鼠LC区神经元Fos表达增加,吗啡依赖大鼠纳酪酮(4mg/Kg,ip)催促戒断后,Fos表达进一步增加;鞘内注射M_2受体和GDNF反义寡脱氧核苷酸处理后均减少吗啡戒断大鼠LC区神经元Fos表达(n=5,P<0.05)。而鞘内注射M_1受体反义寡脱氧核苷酸处理组LC 区神经元Fos表达较吗啡戒断组没有显著差异(n=5,P>O.05)。结果提示:脊髓M_2受体调节吗啡戒断时LC区的神经元激活,而这种神经上行性激活涉及神经元与胶质细胞之间的适应性调节。     

Mu receptor-serotonin link in opioid induced hyperactivity in mice

Opioid induced locomotor excitation in mice was studied. Both morphine and fentanyl increased spontaneous locomotor activity (SLA). Pentazocine produced a significant inhibition of SLA and also blocked the effects of subsequent morphine and fentanyl, thereby underscoring the importance of mu receptors for the opioid induced enhancement of SLA. Serotonergic receptor blockade with cyproheptadine or depletion with fenfluramine blocked, while uptake blockade with clomipramine potentiated the excitatory effect of fentanyl. Thus a mu receptor-serotonin link for the expression of opioid induced locomotor excitation becomes evident.     

Increased glutamate synaptic transmission in the nucleus raphe magnus neurons from morphine-tolerant rats

Currently, opioid-based drugs are the most effective pain relievers that are widely used in the treatment of pain. However, the analgesic efficacy of opioids is significantly limited by the development of tolerance after repeated opioid administration. Glutamate receptors have been reported to critically participate in the development and maintenance of opioid tolerance, but the underlying mechanisms remain unclear. Using whole-cell voltage-clamp recordings in brainstem slices, the present study investigated chronic morphine-induced adaptations in glutamatergic synaptic transmission in neurons of the nucleus raphe magnus (NRM), a key supraspinal relay for pain modulation and opioid analgesia. Chronic morphine significantly increased glutamate synaptic transmission exclusively in one class of NRM cells that contains μ-opioid receptors in a morphine-tolerant state. The adenylyl cyclase activator forskolin and the cAMP analog 8-bromo-cAMP mimicked the chronic morphine effect in control neurons and their potency in enhancing the glutamate synaptic current was significantly increased in neurons from morphine-tolerant rats. MDL12330a, an adenylyl cyclase inhibitor, and H89, a protein kinase A (PKA) inhibitor, reversed the increase in glutamate synaptic transmission induced by chronic morphine. In addition, PMA, a phorbol ester activator of protein kinase C (PKC), also showed an increased potency in enhancing the glutamate synaptic current in these morphine-tolerant cells. The PKC inhibitor GF109203X attenuated the chronic morphine effect. Taken together, these results suggest that chronic morphine increases presynaptic glutamate release in μ receptor-containing NRM neurons in a morphine-tolerant state, and that the increased glutamate synaptic transmission appears to involve an upregulation of both the cAMP/PKA pathway and the PKC pathway. This glutamate-mediated activation of these NRM neurons that are thought to facilitate spinal pain transmission may contribute to the reduced opioid analgesia during opioid tolerance.     

基底外侧杏仁核对睡眠-觉醒的调节作用

采用多道睡眠描记方法,观察了基底外侧杏仁核在睡眠－觉醒调节中的作用。结果发现,电损毁双侧ＢＬＮ引起慢波睡眠和快波睡眠增加,觉醒减少;在双侧ＢＬＮ内注射选择性损毁神经元胸体剂量的红藻氨酸引起双相效应,注射ＫＡ后第１天出现失眠,自第３天开始,ＳＷＳ增多,Ｗ减少,但ＰＳ无显著变化。     

Effect of apomorphine on the wakefulness-sleep cycle of the common frog <Emphasis Type="Italic">Rana temporaria</Emphasis>

This work considers effects of introduction into spinal lymphatic sac of dopamine agonist-apomorphine (APO)-at doses of 0.1, 1.0, 2.0, and 4.0 mg/kg body weight on the common frog wakefulness-sleep cycle (WSC). Usually the frog WSC is represented by wakefulness and three types of passive-protective behavior: the immobility states of the type of catalepsy, catatonia, and cataplexy that are characterized by high thresholds of arousal and by different (corresponding to the name) skeletal muscle tones. These immobility forms are considered as homologues of mammalian stressreaction, hibernation, and sleep. Low apomorphine doses produced in WSC a marked decrease of portion of wakefulness and an increase of the immobility state of the catalepsy type; high doses, on the contrary, initially promoted in CNS an increase of wakefulness and the state of catalepsy by demonstrating thereby its stressogenic action; after this, in WSC there increased the portion of the sleep-like immobility state of the catalepsy type that is considered a functional homologue of sleep of homoiothermal animals. In spectra of electrograms of the frog telencephalon the representation of waves of the delta diapason rose. Taking into account that the states of catalepsy and cataplexy in frogs are under control of anterior hypothalamus, it can be suggested that manifestations of cataplexy (sleep) in frog are due to the low level of dopaminergic activity, whereas manifestations of catalepsy (the homologue of stress reaction) are due to the high dopamine content in the anterior hypothalamic structures. Comparative analysis of changes in WSC of amphibians and mammals in response to administration of dopamine and its agonists allows thinking that the role of the dopaminergic neurotransmitter system in regulation of the vertebrate WSC certainly consists in that the low level of activity of this system facilitates development of sleep (catalepsy), whereas the high level provides reaction of arousal and is actively included in the system providing stress-reaction.     

Induction of wakefulness and inhibition of active (REM) sleep by GABAergic processes in the nucleus pontis oralis

The present study was undertaken to explore the role of brainstem GABAergic processes in the control of the behavioral states of sleep and wakefulness, and to compare the effects of GABAA agonists and antagonists with those of GABAB agonists and antagonists on these behavioral states. Accordingly, the following drugs were microinjected into the nucleus pontis oralis (NPO) in chronic, unanesthetized cats: muscimol (GABAA agonist), bicuculline (GABAA antagonist), baclofen (GABAB agonist) and phaclofen (GABAB antagonist). The percentage, latency, frequency and duration of each behavioral state were measured in order to quantify the effects of these microinjections on wakefulness and sleep. Microinjections of either muscimol or baclofen immediately induced wakefulness. There was a significant increase in the duration and the percentage of time spent in wakefulness as well as an increase in the latency to active (REM) sleep. These changes were accompanied by a decrease in the percentage of time spent in active and quiet sleep. In contrast, injections of bicuculline or phaclofen produced active sleep. The percentage of time spent in active sleep and the frequency of active sleep increased while the percentage of time spent in wakefulness and the latency to active sleep was significantly reduced. The effects of GABAA receptor agonists and antagonists on wakefulness and active sleep were comparable, but stronger than those of GABAB receptor agonists and antagonists. These data indicate that pontine GABAergic processes acting on both GABAA and GABAB receptors play a critical role in generating and maintaining wakefulness and in controlling the occurrence of state of active sleep.     

Different affective response to opioid withdrawal in adolescent and adult mice

AimsDrug withdrawal is suggested to play a role in precipitating mood disorders in individuals with familial predisposition. Age-related differences in affective responses to withdrawal might explain the increased risk of mental illnesses when drug use begins during adolescence. Since there is a lack of animal research examining the effects of opioid withdrawal during adolescence, the present study examined whether there are age-related differences in affective responses to opioid withdrawal.Main methodsAdolescent and adult mice were injected with two different morphine regimens, namely low and high, which differed in the dosage. Three and nine days following discontinuation of morphine administration, immobility time in the forced swim test (FST) and locomotion (total distance traveled) were evaluated.Key findingsOn withdrawal day 3 (WD3), adolescent mice exhibited a decrease in immobility as compared to controls. No significant differences in immobility were observed on withdrawal day 9 (WD9). This effect on FST behaviors was not due to changes in overall motor activity, since no differences in locomotion were observed on either WD3 or WD9 in adolescent mice. In adults, no differences in either FST or locomotor behaviors were observed on WD3. As expected, on WD9, adult mice exhibited an increase in immobility and a decrease in locomotion.SignificanceThis study demonstrates age-dependent differences in both FST scores and locomotor behaviors during opioid withdrawal. FST behaviors are classically used to evaluate mood in rodents, thus this study suggests that opioid withdrawal might affect mood differentially across age.     

Modification of the effects of naloxone in morphine-dependent mice

Mice were rendered dependent on morphine by mixing morphine with their food (2 mg/g) for three days. Increasing doses of naloxone precipitated dose-dependent withdrawal reactions such as weight loss and jumping. These withdrawal reactions were antagonized by morphine pretreatment. Effects of morphine, such as increased locomotor activity, inhibition of intestinal transport, and analgesia were antagonized by naloxone in both non-dependent and dependent subjects. The antagonist actions of naloxone were increased in dependent subjects; lower doses of naloxone were sufficient to antagonize effects of morphine. The present results confirm earlier studies indicating that precipitation of withdrawal can be antagonized by morphine pretreatment suggesting that withdrawal reactions are due to actions of naloxone at the same receptor at which opioid agonists act. The increased antagonist potency of naloxone in dependent subjects extends earlier results obtained with analgesic effects to several other agonist effects of morphine and is consistent with the interpretation that exposure to an opioid agonist induces a change in the conformation of opioid receptors.     

Intramuscular and esophageal electrode recordings of posterior cricoarytenoid activity in normal subjects

Six normal human subjects were studied to compare intramuscular and esophageal electrode recordings of posterior cricoarytenoid (PCA) muscle activity. A new electromyographic technique was developed to implant hooked wire electrodes into the PCA via a nasopharyngoscope. The esophageal electrode was similar to that used by other investigators to record PCA activity (P. C. Kosch et al. J. Appl. Physiol. 64: 1968-1978, 1988). Simultaneous recordings from the intramuscular and esophageal electrodes were obtained during wakefulness and sleep. Changes in esophageal electrode activity were compared with changes in intramuscular electrode activity under four conditions: 1) voluntary maneuvers, 2) differences in state, 3) nasal airway occlusion during non-rapid-eye-movement sleep, and 4) spontaneous variations in respiratory efforts during non-rapid-eye-movement or rapid-eye-movement sleep. Although similar results were obtained from the esophageal and intramuscular electrodes, differences were present between the two recordings during both wakefulness and sleep. The esophageal electrode recorded activity from surrounding muscles during voluntary maneuvers, vocalization, and quiet breathing in wakefulness. Discrepancies between the two electrode recordings during sleep occurred under conditions of increased and decreased respiratory motor output. The data suggest that the esophageal electrode may not give an accurate assessment of PCA activity during many conditions in wakefulness and sleep.     

Comparison of opiate- and opioid-peptide-induced immobility.

Intraventricular administration of the endogenous opioid peptide β-endorphin produces a profound state of immobilization in rats characterized by the absence of spontaneous movement, loss of the righting response and extreme generalized muscular rigidity. The immobility syndrome induced by the opioid peptides β-endorphin and D-Met²-Pro⁵-enkephalinamide was compared with the behavioral profile prodced by subcutaneous and intraventricular administration of the opiates, morphine, methadone and etonitazene. The results indicate a close similarity between the pattern of effects caused by the opiates and opioid peptides. The immobility syndrome could also be produced by injection of β-endorphin into the ventromedial periaqueductal gray, but not into the caudate, globus pallidus, amygdala or dorsolateral periaqueductal gray. The resemblance between the opiate- and β-endorphin-induced profiles suggests that their effects are mediated through common mechanisms.     

Effect of apomorphine on the wakefulness--sleep cycle of the common frog Rana temporaria

This work considers effects of introduction into spinal lymphatic sac of dopamine agonist--apomorphine-(APO) at doses of 0.1, 1.0, 2.0 and 4.0 mg/kg body weight on the common frog wakefulness-sleep cycle (WSC). Usually the frog WSC is represented by wakefulness and three types of passive-protective behavior: by immobility states of the type of catalepsy, catatonia, and cataplexy that are characterized by high thresholds of arousal and by different (corresponding to the name) skeletal musculature tones. These immoboloty forms are considered as homologues of mammalian stress-reaction, hibernation, and sleep. Low apomorphine doses produced in WSC a marked decrease of portion of wakefulness and an increase of the immoboloty state of the catalepsy; high doses, on the contrary, initially promoted in CNS an increase of wakefulness and the state of catalepsy by demonstrating thereby its stressogenic action; after this, in WSC these increased the portion of the sleep-like immobility state of the catalepsy type that is considered as a functional homologue of sleep of homoiotherms. In spectra of electrograms of the flog telencephalon the representation of waves of the delta diapason rose. Taking into account that the states of catalepsy and cataplexy in frogs are under control of the anterior hypothalamus, it can be suggested that manifestations of cataplexy (sleep) in frog are due to the low level of dopaminergic activity, whereas manifestations of catalepsy (the homologue of stress reaction) are due to the high dopamine content in the anterioi hypothalamic structures. Comparative analysis of changes in WSC of amphibians and mammals in response to administration of dopamine and its agonists allows thinking that the role of the dopaminergic neurotransmitter system in regulation of the vertebrate WSC is unanimous: the low level of activity of this system facilitates development of sleep (catalepsy), whereas the high level provides reaction of arousal and is actively included in the system providing stress-reaction.