P物质、亮氨酸脑啡肽、5-羟色胺样成分在新生儿中脑导水管周围灰质的分布

本文用PAP和ABC法对3例生后1—2天新生儿中脑导水管周围灰质(PAG)内P物质、亮氨酸脑啡肽、5-羟色胺样成分的分布进行了观察。发现P物质样阳性胞体主要位于PAG的中、尾段,分为位于腹外侧区的腹侧群和位于腹外侧区与背外侧区交界处的外侧群等两群。其阳性纤维和终末以背侧区为最密。亮氨酸脑啡肽样阳性胞体也出现于PAG中、尾段的各个区内,以腹外侧区数量为多,其阳性纤维及终末也以腹外侧区最密集。5-羟色胺样阳性胞体集中在PAG中、尾段的腹外侧区,其阳性纤维及终末主要分布于PAG的内侧区。本文还对此三种物质与镇痛机制的关系进行了讨论。     

Effects of intrathecal substance P and a substance P antagonist on a reflex to noxious heat are independent of changes in tail skin temperature

Substance P or the substance P receptor antagonist (d-Arg¹, d-Trp^{7, 9}, Leu¹¹)-substance P (Spantide) was injected into the lumbar subarachnoid space in mice, and the ability to change the tail-flick reflex and the tail skin temperature was investigated. Tail-flick latency (the time needed to evoke the tail-flick reflex by noxious radiant heat) was reduced for 1–4 min after intrathecal administration of substance P (5 μg), but the tail skin temperature was not significantly changed. Nor was the tail skin temperature significantly changed after intrathecal injection of Spantide (5 pg), but this compound significantly increased tail-flick latencies 5–30 min after injection. Analysis of co-variance showed that the effects of substance P or Spantide on tail-flick latency were significant, whereas the influence of tail skin temperature on tail-flick latency was nonsignificant. Thus, intrathecal substance P induces a short-lasting increase in nociceptive sensitivity, and intrathecal Spantide produces an antinociceptive effect of longer duration. The results seem not to be the result of changes in tail skin temperature.     

Regionally defective colonization of the terminal bowel by the precursors of enteric neurons in lethal spotted mutant mice

In order to gain insight into the process of colonization of the bowel by the neural crest-derived precursors of enteric neurons, the development of the enteric nervous system was examined in lethal spotted mutant mice, a strain in which a segment of bowel is congenitally aganglionic. In addition, nerve fibers within the ganglionic and aganglionic zones of the gut of adult mutant mice were investigated with respect to their content of acetylcholinesterase, immunoreactive substance P, vasoactive intestinal polypeptide and serotonin, and their ability to take up [³Hserotonin. In both the fetal gut of developing mutant mice and in the mature bowel of adult animals abnormalities were limited to the terminal 2 mm of colon. The enteric nervous system in the proximal alimentary tract was indistinguishable from that of control animals for all of the parameters examined. In the terminal bowel, the normal plexiform pattern of the innervation and ganglion cell bodies were replaced by a coarse reticulum of nerve fibers that stained for acetylcholineserase and were continuous with extrinsic nerves running between the colon and the pelvic plexus. These coarse nerve bundles contained greatly reduced numbers of fibers that displayed substance P- and vasoactive intestinal polypeptide-like immunoreactivity, but a serotonergic innervation was totally missing from the aganglionic bowel. During development, acetylcholineserase and uptake of [³Hserotonin appeared in neural elements in the foregut of mutant mice on the 12th day of embryonic life (E12), about the same time these markers appeared in the forgut in normal mice. By day E14, neurons expressing one or the other marker were recognizable as far distally as about 2 mm from the anus. The appearance of neurons in segments of gut grown for 2 weeks as expiants in culture was used as an assay for the presence of neuronal progenitor cells in the segments of fetal bowel at the time of explantation. Both acetyl- cholinesterase activity and uptake of [³Hserotonin developed in neuronsin vitro in expiants of proximal bowel between days E10 and E17. At all times, however, the terminal 2mm of mutant but not normal fetal gut gave rise to aneuronal cultures. In some mutant mice rare, small, ectopically-situated pelvic ganglia were found just outside aganglionic segments of fetal colon. Uptake of [³Hserotonin, normally a marker for intrinsic enteric neurites, was found in these ganglia.The experiments suppport the hypothesis that the terminal 2 mm of the gut in lethal spotted mutant mice is intrinsically abnormal and thus cannot be colonized by the precursors of enteric neurons. The defect seems to be specific in that both cells and processes of intrinsic enteric neurons, including all serotonergic and most peptidergic neurites, seem to be excluded from the abnormal region while extrinsic nerve fibers, including sympathetic and sensory axons, are able to enter the aganglionic zones. Since examination of neural progenitor cells has failed to reveal a significant proximo-distal displacement of these cells through the enteric tube during development of the murine bowel, a defect in the migration of precursor cells down the alimentary tract to the terminal gut seems unlikely to be substantially involved in the pathogenesis of aganglionosis. This conclusion is supported by the normal enteric nervous system in proximal regions of the mutant gut and the presence of enteric type neurons outside of, but at the same level as the aganglionic region.     

Psychiatric comorbidity of smoking and nicotine dependence

Recent epidemiologic studies have revealed that comorbidity of psychiatric disorders is far more pervasive than previously suspected. Strong associations have been reported between specific substance use disorders and between any mental disorder and any substance use disorder. This report focuses on comorbidity of nicotine dependence, a substance use disorder on which little epidemiologic information is available. Data come from an epidemiologic study of approximately 1000 young adults in southeast Michigan, in which the NIMH-DIS, revised according to DSM-III-R, was used. Lifetime prevalence of nicotine dependence was 20%. Males and females with nicotine dependence had increased odds for alcohol and illicit drug disorders, major depression, and anxiety disorders, compared with nondependent smokers and nonsmokers combined. Major depression and any anxiety disorder were associated specifically with nicotine dependence. Increased odds for alcohol or illicit drug disorders were observed also in nondependent smokers, compared to nonsmokers. History of early conduct problems increased the odds for nicotine dependence among smokers. Potential mechanisms in the comorbidity of nicotine dependence are discussed.     

Substance P and somatostatin metabolism in sympathetic and special sensory ganglia in vitro

Mechanisms regulating the content of the putative peptide transmitters, substance P and somatostatin, were examined in several neuronal populations in culture. Substance P levels increased more than 25-fold within 48 h in sympathetic neurons in the explanted rat superior cervical ganglion, and remained elevated for 4 weeks. Identity of the peptide was authenticated by combined high pressure liquid chromatography-radioimmunoassay. Veratridine prevented the increase of substance P in vitro, and tetrodotoxin blocked the veratridine effect, suggesting that sodium ion influx and membrane depolarization prevent peptide elevation. Veratridine (or potassium)-induced membrane depolarization released substance P into the culture medium through a calcium-dependent process. Consequently, at least some veratridine effects are attributable to release and subsequent depletion of ganglion peptide. However, the inhibitory effects of veratridine were far greater than could be accounted for by the quantity of peptide released, suggesting a separate influence on net synthesis (synthesis less catabolism) of substance P. Viewed in conjunction with previous in vivo studies, our observations suggest that trans-synaptic impulses, through the mediation of postsynaptic sodium flux, release substance P from sympathetic neurons and also regulate intracellular peptide metabolism. To determine whether the processes regulating substance P in sympathetic neurons reflect generalized mechanisms, a different peptide, somatostatin, was examined in sympathetic neurons; moreover, substance P was examined in a different neuronal population, special sensory neurons in the nodose ganglion. Substance P levels increased significantly in both sympathetic and sensory neurons after explantation, and somatostatin levels increased in sympathetic neurons. In each instance, the increase was dependent upon the presence of the calcium ions. Moreover, these increases were all prevented by veratridine, in a tetrodotoxin-sensitive manner. Our observations suggest that common regulatory mechanisms govern peptide transmitter metabolism in diverse neuronal populations.     

Effect of peripheral axotomy on the fine structure and histochemistry of the Rolando substance: Degenerative atrophy of central processes of pseudounipolar cells

Summary Disappearence of fluorid-resistant acid phosphatase activity from the ipsilateral Rolando substance after transection of the peripheral nerve, is shown to be due to the cessation of enzyme supply from dorsal root ganglion cells to their central terminals. This is accompanied by (or ensues in consequence of) a fine structural derangement of these terminals (degenerative atrophy). Fine structural alterations of axon terminals undergoing degenerative atrophy, though similar to some extent to those seen during early phases of a Wallerian degeneration, are markedly different. Also myelinated nerve fibers, both in the dorsal horn and in dorsal columns, are affected by degenerative atrophy. This important, new trophical feature of sensory ganglion cells suggests a delicate metabolic balance between peripheral and central axonal branches of bipolar (pseudounipolar) cells. Degenerative atrophy raises serious implications in evaluating hodological experiments based upon Wallerian degeneration and offers new perspectives for theoretical and clinical neurology.     

湖南省两地区成瘾物质使用状况调查报告：使用率及相关因素

本文采用整群抽样的方法，对湖南两地区城乡共２３７７人（１５岁以上）的成瘾物质使用状况进行调查，其中男１１７９（４９．６％）人，女１１９９（５０．４％人），平均年龄男女分别为４１．２（ＳＤ＝１７．５）和４３．４（ＳＤ＝１８．６）。结果表明，饮酒率男性为５７．５％，女性为１７．３％，吸烟率男女分别为６８．２％和１１．７％；饮酒者多集中在每月饮１次左右的人群中（男５７．９％，女７７．９％），但吸烟者多集中在每日吸２０支及以上（男５２．４％，女４２．９％）的人群中。除解热镇痛剂外，男性各种精神活性物质的使用频率及剂量皆男高于女性，开始使用的年龄及成瘾的年龄男性低于女性；性别、使用频度、最早使用的年龄、婚姻与饮酒、吸烟量关系最为密切。有１４人使用过鸦片类物质，４人使用过兴奋剂。作者讨论了我国成瘾物质使用的特点，指出经济水平、社会文化背景等因素与我国社会性成瘾物质的使用有密切关系。     

GABA(A) receptor facilitation of neurokinin release from primary afferent terminals in the rat spinal cord

Our goal was to test the following hypotheses: 1) GABA_A receptors facilitate neurokinin release from primary afferent terminals; 2) they do this by suppressing an inhibitory effect of GABA_B receptors; 3) the activation of these two receptors is controlled by the firing frequency of primary afferents. We evoked neurokinin release by stimulating the dorsal root attached to spinal cord slices, and measured it using neurokinin 1 receptor (NK1R) internalization. Internalization evoked by root stimulation at 1 Hz (but not at 100 Hz) was increased by the GABA_A receptor agonists muscimol (effective concentration of drug for 50% of the increase [EC₅₀] 3 μM) and isoguvacine (EC₅₀ 4.5 μM). Internalization evoked by root stimulation at 100 Hz was inhibited by the GABA_A receptor antagonists bicuculline (effective concentration of drug for 50% of the inhibition [IC₅₀] 2 μM) and picrotoxin (IC₅₀ 243 nM). Internalization evoked by incubating the root with capsaicin (to selectively recruit nociceptive fibers) was increased by isoguvacine and abolished by picrotoxin. Therefore, GABA_A receptors facilitate neurokinin release. Isoguvacine-facilitated neurokinin release was inhibited by picrotoxin, low Cl⁻, low Ca²⁺, Ca²⁺ channel blockers and N-methyl-d-aspartate receptor antagonists. Bumetanide, an inhibitor of the Na⁺-K⁺-2Cl⁻ cotransporter, inhibited isoguvacine-facilitated neurokinin release, but this could be attributed to a direct inhibition of GABA_A receptors. The GABA_B agonist baclofen inhibited NK1R internalization evoked by 100 Hz root stimulation (IC₅₀ 1.5 μM), whereas the GABA_B receptor antagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl) phosphinic acid (CGP-55845) increased NK1R internalization evoked by 1 Hz root stimulation (EC₅₀ 21 nM). Importantly, baclofen inhibited isoguvacine-facilitated neurokinin release, and CGP-55845 reversed the inhibition of neurokinin release by bicuculline. In conclusion, 1) GABA_B receptors located presynaptically in primary afferent terminals inhibit neurokinin release; 2) GABA_A receptors located in GABAergic interneurons facilitate neurokinin release by suppressing GABA release onto these GABA_B receptors; 3) high frequency firing of C-fibers stimulates neurokinin release by activating GABA_A receptors and inhibiting GABA_B receptors, whereas low frequency firing inhibits neurokinin release by the converse mechanisms.     

大鼠蓝斑内P物质、神经降压肽和生长抑素样神经元的上行投射

本实验采用HRP逆行追踪与免疫细胞化学相结合的方法,对大鼠蓝斑内P物质(SP)、神经降压肽(NT)、生长抑素(SOM)三种肽能投射神经元的纤维联系及其局部关系进行了探讨。结果证实:1.HRP注射至丘脑或尾壳核后,大鼠蓝斑内均可见到双标记神经元。2.存在SP样和NT样蓝斑—丘脑纤维,前者终止于丘脑腹后核和板内核,后者终止于丘脑板内核。3.蓝斑至尾壳核的投射呈SOM样免疫反应。4.蓝斑内三种肽能投射的起始和终止部位有所不同,其中SP样和NT样神经元主要位于蓝斑后部背侧区,其纤维终于丘脑;而SOM样投射神经元则见于蓝斑前部背侧区,纤维终止于尾壳核。上述肽能通路均为双侧性,而以同侧占优势。5.蓝斑内三种肽能单标记神经元中以NT样免疫反应阳性胞体最为丰富。以上结果表明;蓝斑上行性投射中除含去甲肾上腺素纤维外,还含有SP样、NT样和SOM样纤维,并存在一定的局部定位投射关系。