出血性卒中脑脊液环核苷酸变化的研究

放免法测定４６例出血性卒中患者（蛛网膜下腔出血３０例，脑出血１６例）脑脊液环磷酸腺苷（ｃＡＭＰ）和环磷酸鸟苷（ｃＧＭＰ）含量的变化，并与２０例外科病人作对照。结果发现出血性卒中急性期脑脊液的ｃＡＭＰ和ｃＧＭＰ含量明显高于对照组（Ｐ＜０．０１～０．０５）。文中对引起这种改变的机理及其临床意义进行了讨论。     

实验性癫痫大鼠海马结构内一氧化氮-环磷酸鸟苷途径的研究

目的研究实验性癫痫发作大鼠海马结构内一氧化氮（ＮＯ）环磷酸鸟苷（ｃＧＭＰ）信使机制及其意义。方法雄性ＳＤ大鼠４１只，随机分为对照组（５只）、红藻氨酸（ＫＡ）１０、３０、６０分钟组（每组６只）和Ｌ硝基精氨酸甲酯（ＬＮＡＭＥ）＋ＫＡ１０、３０、６０分钟组（每组６只）。用放射免疫法测定ＫＡ诱导性癫痫发作中各时点海马结构内ｃＧＭＰ含量及ＬＮＡＭＥ的干预效应。结果ＫＡ注射引起大鼠海马结构内ｃＧＭＰ浓度升高，并加重大鼠癫痫发作（湿狗样摇动提早出现和发生次数增多）；ＫＡ注射前３０分钟给予ＬＮＡＭＥ可明显抑制ＫＡ１０、３０分钟组ｃＧＭＰ浓度的升高，但ＬＮＡＭＥ对ＫＡ６０分钟组ｃＧＭＰ的抑制作用不显著。结论在ＫＡ发作早期，ｃＧＭＰ浓度升高与内源性ＮＯ有关；ＮＯ的抗发作效应可能与ｃＧＭＰ信使机制存在某种联系。     

缺血性脑卒中患者脑脊液cAMP、cGMP测定

缺血性脑卒中患者脑脊液ｃＡＭＰ、ｃＧＭＰ测定李善宗，钱采韵环磷腺苷（ｃＡＭＰ）、环磷鸟苷（ｃＧＭＰ）是通过腺苷酸环化酶及鸟苷酸环化酶合成的具有媒介多种生物活性物质对细胞作用从而产生一系列生物效应的“第二信使”。动物研究证明中枢神经疾患时脑内ｃＡＭＰ、...     

偏头痛和慢性紧张型头痛血浆精氨酸加压素、催产素及环核着酸含量测定

用放射免疫分析法测定了２８例偏头痛、１０例慢性紧张型头痛患者和１６例健康对照组血浆精氨酸加压素（ＡＶＰ）、催产素（ＯＴ）、环磷酸腺苷（ｃＡＭＰ）及环磷酸鸟苷（ｃＧＭＰ）含量。结果表明，偏头痛发作期ＡＶＰ含量下降、ｃＡＭＰ含量升高，偏头痛间歇期ｃＧＭＰ含量下降，血浆ＯＴ含量在发作期和间歇期均明显下降。慢性紧张型头痛患者血浆ＡＶＰ、ＯＴ、ｃＡＭＰ和ｃＧＭＰ与对照组比较均无显著性差异。结果提示，血浆ＡＶＰ和ＯＴ水平降低以及环核苷酸的代谢异常与偏头痛发病机制有关。     

强啡肽和苯环利定在高血压大鼠的环腺苷酸生成系统中的作用

采用放射免疫检测方法，观察了强啡肽（Ｄｙｎ）和苯环利定（ＰＣＰ）对高血压大鼠（ＳＨＲ）的环腺苷酸（ｃＡＭＰ）生成系统的影响，结果表明：Ｄｙｎ剂量依赖地降低ＳＨＲ和非高血压大鼠（ＷＫｙ）的外周血管中ｃＡＭＰ的含量，并且对ＳＨＲ的ｃＡＭＰ生成系统的抑制作用大于ＷＫｙ（Ｐ〈０．０５），相反地，ＰＣＰ剂量依赖地升高ＳＨＲ和ＷＫｙ的外周血管中的ｃＡＭＰ的含量，对ＳＨＲ的ｃＡＭＰ生成系统的激活作用小于ＷＫｙ（     

生长抑素调节疑核神经兴奋性氨基酸受体介导的兴奋

在含有孤束中央亚核（ＮＴＳｃ）疑核神经元密集区（ＡＭＢｃ）及孤束－疑核传导束的脑片，注射生长抑素（ＳＳＴ）于ＡＭＢｃ区，对Ｎ－ｍｅｔｈｙｌ－Ｄ－ａｓｐａｒｔａｔｅ（ＮＭＤＡ）引起的疑核神经元膜电位去极化有易化作用，而注射ｃｙｓｔｅａｍｉｎｅ耗竭内源性ＳＳＴ后，ＮＭＤＡ的去极化作用减弱；ＮＭＤＡ受体阻断剂Ｄ，Ｌ－２－ａｍｉｎｏ－７－ｐｈｏｓｐｈｏｎｏｈｅｐｔａｎｏｉｃａｃｉｄ（ＡＰ－７）使疑核神经元     

生长抑素调节疑核神经元兴奋性氨基酸受体介导的兴奋

在含有孤束核中央亚核（ＮＴＳｃ）疑核神经元密集区（ＡＭＢｃ）及孤束─疑核传导束的脑片，注射生长抑素（ＳＳＴ）于ＡＭＢｃ区，对Ｎ—ｍｅｔｈｙｌ—Ｄ－ａｓｐａｒｔａｔｅ（ＮＭＤＡ）引起的疑核神经元膜电位去极化有易化作用，而注射ｃｙｓｔｅａｍｉｎｅ耗竭内源性ＳＳＴ后，ＮＭＤＡ的去极化作用减弱；ＮＭＤＡ受体阻断剂Ｄ，Ｌ—２—ａｍｉｎｏ—７一ｐｂｏｓｐｈｏ－ｎｏｈｅｐｔａｎｏｉｃａｃｉｄ（ＡＰ─７）使疑核神经元兴奋性突触后电位（ＥＰＳＰ）幅度降低，而ＳＳＴ可翻转ＡＰ—７的抑制效应；对ｎｏｎ—ＮＭＤＡ介导的疑核神经元膜去极化，ｃｙｓｔｅａｍｉｎｅ亦对其有明显抑制作用；甘氨酸（ｇｌｙｃｉｎｅ）可阻断ＳＳＴ易化疑核神经元的去极化作用。这些结果表明，ＳＳＴ对疑核神经元兴富性氨基酸（ＥＡＡ）受体介导的兴奋起重要的调节作用。     

大鼠脑缺血再灌流脑区一氧化氮变化的研究

目的研究大鼠脑缺血及再灌流后脑部一氧化氮的变化。方法采用荧光法和放射免疫法测定４个脑区一氧化氮（ＮＯ）代谢产物ＮＯ２和环磷酸鸟苷（ｃＧＭＰ）。结果脑缺血１０ｍｉｎ,各脑区ＮＯ２和ｃＧＭＰ含量明显增高;脑缺血３０ｍｉｎ,各脑区ＮＯ２和ｃＧＭＰ含量开始下降。缺血１０ｍｉｎ再灌流１５ｍｉｎ以及缺血３０ｍｉｎ再灌流１５ｍｉｎ,各脑区ＮＯ２和ｃＧＭＰ含量再次增加,与单纯脑缺血组相比,有显著差异性（Ｐ＜０．０５或Ｐ＜０．０１）。结论ＮＯ参与了脑缺血再灌流的损伤过程     

中脑导水管周围灰质和海马在ACTH镇痛中的相互关系

以往工作发现，中脑导水管周围灰质（ＰＡＧ）和海马在非阿片肽ＡＣＴＨ痛觉调制中占有重要地位。但它们之间的相互影响在ＡＣＴＨ痛觉调制中的作用，尚未阐明。本工作利用免疫组织化学和病阈测定方法，进一步观察大鼠ＰＡＧ和海马在ＡＣＴＨ镇痛时的相互关系，并与吗啡镇痛作用相比较。结果如下：（１）海马内注射ＡＣＩＨ（０．５ｕ／４μｌ）或吗啡（５μｇ／４μｌ），痛阈明显升高（１１９．３±４．７％，１２２．７±２６．８％）与对照组比较有显著差异（Ｐ＜０．０１），该明显效应均可被ＰＡＧ内注射阿片受体拮抗剂纳络酮所阻断；（２）ＰＡＧ内注射吗啡或ＡＣＴＨ后病阈提高更显著（１８０．９±５０．３％，２１９．８±７７．０％，Ｐ＜０．０１），但海马内注射纳络酮可阻断前者的效应（Ｐ＜０．０５）而对后者却无影响（Ｐ＞０．０５）；（３）伤害性刺激福尔马林（Ｆ）可诱发大鼠脊髓腰膨大背角原癌基因ｃ－ｆｏｓ显著表达，以Ⅰ、Ⅱ层较显著，海马或ＰＡＧ内注射ＡＣＴＨ均可抑制其背角ｃ－ｆｏｓ表达。结果提示：ＰＡＧ、海马均参与ＡＣＴＨ和阿片系统对脊髓痛信息传递的调制作用，在ＡＣＴＨ痛觉调制作用中，表明ＰＡＧ、海马之间的相互影响是复杂的。     

GMP—140与脑血栓形成的关系研究

目的探讨急性脑血栓形成不同时期ＧＭＰ－１４０含量的变化。方法测定３２例急性脑血栓患者病后３ｄ内血浆中ＧＭＰ－１４０、ＳＯＤ和ＭＤＡ的含量，其中２５例患者于病程第１０～１４ｄ再次抽血复查。另选２８例性别、年龄组成相似的动脉硬化患者作为对照。结果与动脉硬化组比较，脑血栓患者急性期血浆中ＧＭＰ－１４０和ＭＤＡ含量显著增高（Ｐ＜０．０５），ＳＯＤ含量显著降低（Ｐ＜０．０５）；至稳定期，脑血栓患者血浆中ＧＭＰ－１４０、ＭＤＡ和ＳＯＤ含量与脑动脉硬化组无显著差异（Ｐ＞０．０５）。结论急性脑血栓形成时ＧＭＰ－１４０含量增高与脑组织损伤有关     

Modulation of serotonergic projection from dorsal raphe nucleus to basolateral amygdala on sleep-waking cycle of rats

Putative serotonergic dorsal raphe nucleus (DRN) neurons display a dramatic role in the modulation of behavior. However, it is not clear how this modulation is mediated. The present study investigated the modulatory effects of serotonergic projection of the DRN to the basolateral amygdala (BLA) on the sleep-waking cycle using polysomnograph (PSG) in rats. DRN microinjection of kainic acid (KA) caused insomnia immediately. From the third day, however, slow wave sleep (SWS) and paradoxical sleep (PS) increased markedly. DRN microinjection of p-chlorophenylalanine (PCPA, once a day for 2 days), which inhibits the synthesis of serotonin (5-HT), led to similar effect to KA administration. The percent of sleep-wakefulness began to change on the third day after PCPA microinjection into the DRN, and the effect was most significant on the sixth day. The percent of sleep-wakefulness started to resume on the seventh day. SWS and PS were reduced after excitation of DRN neurons by microinjection of L-glutamate (L-Glu) into the DRN. Preapplication of the nonselective 5-HT receptor antagonist methysergide (MS) into bilateral BLA blocked the effect of DRN microinjection of L-Glu. Furthermore, bilateral BLA microinjection of 5-hydroxytryptophan (5-HTP), the precursor of 5-HT, on the sixth day after microinjection of PCPA into the DRN, could reverse the effect of PCPA microinjection. These results indicate that the modulation of the DRN on sleep is partially mediated by the serotonergic projection of the DRN to the BLA.     

Neurochemical studies on the mesolimbic circuitry of antinociception

Previous studies using the technique of microinjection into brain nuclei indicated that the periaqueductal gray (PAG), nucleus accumbens, habenula and amygdala play an essential role in pain modulation and that these nuclei possibly act through a ‘mesolimbic neural loop‘ to exert an analgesic effect, in which Met-enkephalin (MEK) and β-endorphin (β-EP) have been implicated as the two major opioid peptides involved in antinociception. In the present study performed in rabbits, intracranial microinjection was supplemented with push-pull perfusion and radioimmunoassay to determine whether the release of enkephalins (ENK) and β-EP was increased in these nuclei when the putative neural circuit was activated by morphine administered into one of the nuclei. The results showed: (1) microinjection of morphine into the PAG increased the release of ENK and β-EP in the N. accumbens, and vice versa; (2) microinjection of morphine into the N. accumbens increased the release of ENK and β-EP in the amygdala, and vice versa; (3) morphine microinjected into the PAG caused an increase in the release of ENK and β-EP in the amygdala and vice versa, although the release of ENK in PAG was statistically not significant. These results indicate that PAG, N. accumbens and amygdala are connected in a network served by a positive feedback circuitry.     

Endogenous and exogenous nitric oxide in the pedunculopontine tegmentum induces sleep

Mesopontine cholinergic cells in the pedunculopontine tegmental (PPT) nuclei modulate the control of the wake-sleep cycle by releasing acetylcholine to their target structures. These cells also synthesize nitric oxide (NO) which diffuses into the extracellular space and acts as a neuronal messenger. The present study is based on the hypothesis that NO synthesis and its presence in the extracellular space in the PPT play a functional role in regulating the behavioral states of waking and sleep. This hypothesis was tested by microinjecting a control vehicle, NO donor, S-Nitroso-N-acetyl-penicillamine (SNAP) and a competitive inhibitor of NO synthase enzyme (NOS), N^G-Nitro-L-arginine methylester hydrochloride (L-NAME) into the PPT while quantifying the effects on wakefulness and sleep. Six cats were implanted with bilateral guide tubes for PPT microinjection and with standard electrodes to measure waking, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. Five-hour free-moving polygraphic recordings were made following each microinjection (0.25 μl) of control saline, SNAP or L-NAME. Following microinjection of SNAP into the cholinergic cell compartments of the PPT, SWS and REM sleep were increased by 41.65% and 72.10% respectively, compared to the control microinjection. Microinjection of L-NAME reduced SWS and REM sleep by 40.33% and 62.05%, respectively, compared to controls. The present results demonstrate that endogenous NO synthesized within the PPT cholinergic cells functions as a paracrine signal in the control of waking and sleep by modulating local cholinergic cells. Synapse 27:69–78, 1997. © 1997 Wiley-Liss, Inc.     

Glutamate microinjection at the medial preoptic area enhances slow wave sleep in rats

A large body of evidence has established the role of the medial preoptic area (mPOA) in regulation of slow wave sleep (SWS). Although the mPOA neurons contain excitatory neurotransmitter glutamate, its role in sleep-wakefulness is not known. In the present study microinjection of monosodium glutamate (40, 80 and 120 ng) into the mPOA augmented SWS. Earlier reports have shown enhancement of paradoxical sleep by glutamate in other brain areas.     

Tolerance to non-opioid analgesics in PAG involves unresponsiveness of medullary pain-modulating neurons in male rats

Opiate analgesia can be hampered by a reduction in pharmacological effectiveness (tolerance), and this crucially depends on the periaqueductal gray matter (PAG). Non-opioids like metamizol (dipyrone) or aspirin also induce PAG-dependent analgesia and tolerance, but the neuronal bases of this tolerance are unknown. Metamizol is a pyrazolon derivative and cyclooxygenase inhibitor with widespread use as an analgesic in Europe and Latin America. Metamizol was microinjected into the PAG of awake male rats, and antinociception was assessed by the tail flick (TF) and hot plate (HP) tests. Microinjection twice daily for 2.5 days caused tolerance to metamizol. The rats were then anesthetized and recordings from pain-facilitating on-cells and pain-inhibiting off-cells of the rostral ventromedial medulla (RVM) were performed. PAG microinjection of morphine or metamizol depresses on-cells, activates off-cells and thus inhibits nociception, including TF and HP. In metamizol-tolerant rats, however, PAG microinjection of metamizol failed to affect on- or off-cells, and this is interpreted as the reason for tolerance. In metamizol-tolerant rats morphine microinjection into PAG also failed to affect RVM neurons or nociception (cross-tolerance). In naïve, non-tolerant rats the antinociceptive effect of PAG-microinjected metamizol or morphine was blocked when CTOP, a μ-opioid antagonist, was previously microinjected into the same PAG site. These results emphasize a close relationship between opioid and non-opioid analgesic mechanisms in the PAG and show that, like morphine, tolerance to metamizol involves a failure of on- and off-cells to, respectively, disfacilitate and inhibit nociception. Cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.     

Stimulation-produced spinal inhibition from the midbrain in the rat is mediated by an excitatory amino acid neurotransmitter in the medial medulla

It has been previously established that a bulbar relay plays an important role in descending inhibition of spinal dorsal horn nociceptive neurons and nociceptive reflexes produced by stimulation in the midbrain periaqueductal gray (PAG). In the present study, selected receptor antagonists were microinjected into the medial medullary nucleus raphe magnus (NRM) to determine whether descending inhibition of the tail flick (TF) reflex in the rat produced by focal electrical stimulation in the midbrain PAG was mediated by serotonin, opioid, or glutamate receptors on bulbospinal neurons in the NRM. It was determined in initial experiments that the serotonin receptor antagonist methysergide, the opioid receptor antagonist naloxone, the local anesthetic lidocaine, and the glutamate receptor antagonists gamma-D-glutamylglycine (DGG) and DL-2-amino-5-phosphonovalerate (APV) microinjected into the medulla all significantly increased the threshold of focal electrical stimulation in the medulla required to inhibit the TF reflex. The antinociceptive efficacy of agonists at opioid, serotonin, and glutamate receptors was also tested in other experiments. The microinjection of morphine (2.5-10 micrograms) into the NRM increased significantly TF latencies in a dose-dependent manner in rats in the awake or lightly anesthetized state; morphine was more potent in awake rats. Inhibition of the TF reflex produced by the microinjection of morphine was reversed by a subsequent microinjection of naloxone into the same site in the medulla. The microinjection of serotonin (5 and 10 micrograms), however, did not affect the latency of the TF reflex in either awake or lightly anesthetized rats. Glutamate (100 microM, 0.5 microliter) microinjected into the rostral ventral medulla produced an inhibition of the TF reflex of short duration that could be blocked or attenuated significantly by the glutamate receptor antagonists DGG or APV microinjected into the same site. In subsequent experiments, a nonspecific functional block was introduced adjacent to the NRM bilaterally in the medullary reticular formations (MRFs) by the microinjection of the local anesthetic lidocaine; receptor antagonists were then microinjected into the NRM and their effect on the threshold of focal electrical stimulation in the PAG to inhibit the TF reflex determined. No increase was seen in stimulation thresholds in the PAG following the microinjection of either methysergide or naloxone into the NRM. Following the microinjection of lidocaine, DGG or APV into the NRM, the stimulation threshold in the PAG for inhibition of the TF reflex was increased significantly.(ABSTRACT TRUNCATED AT 400 WORDS)     

PAG mu opioid receptor activation underlies sex differences in morphine antinociception

Given the findings that (1) systemic opioid antinociception varies by estrous stage in females and (2) the magnitude of sex differences in opioid antinociception is negatively correlated with opioid agonist efficacy, we hypothesized that sex differences in the function of the descending pain modulatory system are likely influenced by estrous stage in females and by the number of available opioid receptors therein. The present study tested these hypotheses by (1) comparing antinociception produced by morphine microinjection to the ventral periaqueductal gray (vPAG) in females at different stages of the estrous cycle and (2) examining systemic morphine antinociception in males versus females under conditions of reduced vPAG mu opioid receptor availability. When estrous stage of females was not controlled for (Experiment 1), there was no significant sex difference in tail withdrawal antinociception following morphine microinjection (0.3-10microg), although morphine was more potent in males than females in producing immobility. Experiment 2 showed that intra-vPAG morphine produced less antinociception and immobility in estrus than in diestrus females; that is, only estrus females' response to morphine was lower than that of males. Experiment 3 showed that microinjection of the irreversible mu opioid antagonist beta-funaltrexamine (beta-FNA) into the vPAG shifted the systemic morphine dose-effect curve farther to the right in females than in males. That is, a reduction in available vPAG mu opioid receptors had a greater impact on opioid antinociception in females than in males, suggesting that females have fewer vPAG mu opioid receptors than males. Overall, these data suggest that ovarian hormones and PAG mu opioid receptor density contribute to sex differences in antinociception produced by morphine.     

The effect of modification of 5-hydroxytryptamine function in nucleus raphe magnus on nociceptive threshold

Thresholds to noxious heat stimulation were increased following microinjection of zimelidine, an inhibitor of 5-hydroxytryptamine (5-HT) re-uptake, into the nucleus raphe magnus (NRM) of rats. Pretreatment with intraperitoneally given cinanserin reduced this effect but pretreatment with intraperitoneally given phenoxybenzamine did not. Fenfluramine, which causes the release of 5-HT from synaptic terminals also elevated nociceptive thresholds following microinjection into NRM. Subanalgesic doses of morphine or zimelidine elevated nociceptive thresholds when microinjected together into NRM. The elevation of nociceptive threshold produced by microinjection of morphine into NRM was reduced by simultaneous microinjection of cinanserin into NRM. Cinanserin alone had no effect when microinjected into NRM. These findings suggest that inhibition of the re-uptake of 5-HT in NRM can elevate nociceptive thresholds and that there may be an interaction between the effects of morphine and 5-HT in NRM.     

Effects of selective neuronal nitric oxide synthase inhibition on sleep and wakefulness in the rat

The role played by the unconventional messenger Nitric Oxide (NO) upon the sleep-wake cycle remains controversial. Evidence suggests a positive role of NO on Slow Wave Sleep (SWS) and Paradoxical Sleep (PS) regulation, favoring sleep. However, other studies have found a role of NO upon wakefulness and alertness, inhibiting sleep. Divergences have been explained in part because of the use of different inhibitors of nitric oxide synthases (NOS). The aim of this study is to analyse the effects of a highly selective neuronal NOS inhibitor (3-Bromo7-Nitroindazole) on sleep-wake states in rats. Male Wistar rats were stereotaxically prepared for polysomnography. 3-Bromo-7-Nitroindazole (10, 20, 40 mg/kg, i.p.) dissolved in DMSO 10% filled with saline, or vehicle (DMSO 10% in saline) was administered at the beginning of the light period. Three hours of polygraphic recordings were evaluated for stages of vigilance. Results show dose-dependent effects of 3-Bromo7-Nitroindazole upon sleep: 10 mg/kg decreases duration and number of episodes of deep SWS, increasing duration of light SWS. 20 mg/kg decreased duration of light and deep SWS, while active and quiet wake increased. Deep SWS and PS latency increased. Number of episodes of PS decreased, as well as number of cycles of sleep and time spent asleep. 40 mg/kg reduced duration of deep SWS and increased mean episode duration of light SWS. Therefore, sleep states are affected by selective inhibition of nNOS, reducing in all cases deep SWS. These results support the hypothesis that nitric oxide, produced by nNOS, is involved in sleep processes, favoring sleep.     

腹外侧视前区损毁后结节乳头体核微量注射GABAA受体拮抗剂调控大鼠睡眠-觉醒周期

BACKGROUND： Neurons expressing gamma-aminobutyric acid （GABA） play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tuberomammillary nucleus （TMn）, with regard to the sleep-wakefulness cycle, is poorly understood.
OBJECTIVE： To investigate the effects of GABAergic neurons in the TMn on the sleep-wakefulness cycle.
DESIGN, TIME AND SETTING： Randomized controlled study, performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from July 2007 to February 2008. MATERIALS： Fifteen healthy, adult, male, Sprague Dawley rats were randomly divided into three groups（n = 5）： control, ventrolateral preoptic area （VLPO） lesion, and VLPO lesion plus GABAA receptor antagonist-treated. Ibotenic acid and bicuculline were provided by Sigma （St. Louis, USA）.
METHODS： Four electroencephalogram screw electrodes were implanted into the skull at a frontal region （two） and parietal bones （two） on each side. Three flexible electromyogram wire electrodes were placed into the nuchal muscles. On day 8, a fine glass micropipette （10–20 mm tip diameter） containing ibotenic acid solution （10 nmol/L） was injected into the VLPO in both hemispheres following bone wax removal under anesthesia. One week after the second surgery, sleep-wakefulness states were recorded in rats from the VLPO lesion group. On day 10 after VLPO lesion, bicuculline （10 nmol/L）, a GABAA-receptor antagonist, was microinjected into the TMn and sleep-wakefulness states were recorded for 24 hours.
MAIN OUTCOME MEASURES： Duration of the sleep-wakefulness cycle in each group using a Data acquisition unit （Micro1 401 mk2） and Data collection software （Spike Ⅱ）. RESULTS： VLPO lesion induced an increased duration of wakefulness （W, 13.17%） and light slow-wave sleep （SWS1, 28.9%）, respectively. Deep slow-wave sleep （SWS2, 43.74%） and paradoxical sleep （PS, 44.07%） were respectively decreased for 24 hours at day 9 post-lesion, compared with pre-lesion （P 〈 0.01）. Microinjection of bicuculline into the TMn following VLPO lesion at 10：00 am on the 10th day elicited a wake state for 40–55 minutes, with a latency of 15 minutes. However, 24-hour sleep-wake states demonstrated that the ratio of W and SWS1 were increased by 12.61% （P 〈 0.01） and 50.97% （P 〈 0.01）, respectively. In addition, SWS2 and PS were decreased by 68.08% （P 〈 0.01） and 39.92% （P 〈 0.05）, respectively, compared with prior to VLPO lesion.
CONCLUSION： The evidence of decreased deep slow-wave sleep, which was induced by VLPO lesion, suggested that GABAergic neurons in the VLPO play an important role in maintaining sleep. Bicuculline microinjection into the TMn, following VLPO lesion, elicited wakefulness and sleep depression for 50 minutes, with contrary increased light slow-wave sleep for 24 hours, which suggested that GABAergic neurons in the TMn play a role in sleep drive （sleepiness） via local circuit to directly inhibit histaminergic neurons.