氛氟拉明加强针刺镇痛时前脑啡肽原mRNA的表达(英文)

目的:研究大鼠脑内前脑啡肽原(PPE)mRNA的变化与5-HT的释放剂芬氟拉明加强针刺镇痛的关系.方法:用原位杂交组织化学法观察PPE mRNA的表达.结果:脊髓背角(Ⅰ,Ⅱ层),中缝大核,中缝背核,中央灰质,脚间核,视前外侧区,杏仁核和尾壳核内的PPEmRNA的含量大量升高(P<0.01,vs NS EA),而在隔外侧区,视前内侧区,下丘脑腹内侧核以及脊髓背角Ⅲ—Ⅳ层的PPE mRNA的水平也有中等程度增高(P<0.05,vs NS EA).但在丘脑却没有明显的变化.结论:PPE mRNA含量在与痛相关的区域里增高,是芬氟拉明加强针效的机制之一.     

芬氟拉明合用电针对大鼠脑内中央灰质单胺类释放的影响

研究５－羟色胺释放剂芬氟拉明加强针刺镇痛前后大鼠脑内中央灰质腹侧部单胺类递质的变化 。方法;运用微透析及高效液相电化学检测方法。结果：电针后Ｎｏｒ的释放减少,而５－ＨＴ,５－ＨＩＡＡ和ＤＡ,ＨＶＡ在ＡＧ部位含量升高,当芬氟拉明合用电针时,５－ＨＴ,５－ＨＩＡＡ含量进一步升高,但Ｎｏｒ,ＤＡ及其代谢产物却无明显变化。结论：电针能促进ＤＡ和５－ＨＴ释放但抑制Ｎｏｒ释放。     

舒通安胶囊对海洛因依赖者血单胺类递质的影响

目的:了解5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NE)在海洛因依赖发病中的意义,观察舒通安胶囊对海洛因依赖者单胺类递质的影响。方法:用荧光分光光度法检测56例海洛因依赖者(注射组35例、烫吸组21例)治疗前后和23例正常人血浆及血小板5-HT、5-HIAA、DA和NE含量。结果:海洛因依赖者血浆5-HT、5-HIAA、DA和NE含量均高于对照组(P<0.01),烫吸组血浆DA、5-HIAA含量低于注射组(P<0.05,P<0.01),经舒通安胶囊治疗后血浆5-HT、5-HIAA、DA和NE含量显著降低(P<0.01),其中烫吸组NE高于注射组(P<0.05)。海洛因依赖者血小板5-HT、5-HIAA、DA和NE含量均高于对照组(P<0.01),烫吸组血小板5-HT、DA含量低于注射组(P<0.01),经舒通安胶囊治疗后血小板5-HT、5-HIAA、DA和NE含量显著降低(P<0.01),其中烫吸组DA、5-HT、NE高于注射组(P<0.01,P<0.05)。结论:单胺类递质在海洛因依赖的病理过程可能有重要意义,舒通安胶囊可调节海洛因依赖者外周单胺类递质水平。     

对氨基水杨酸钠对氯化锰染毒大鼠脑单胺递质的影响

本文报道了对氨基水杨酸钠(PAS-Na)对氯化锰腹腔注射染毒大鼠脑单胺递质水平的影响。PAS-Na能使锰染毒所降低了的脑多巴胺(DA)水平逆转;锰使脑去甲肾上腺素(NE)含量增加,染毒后以PAS-Na治疗则使之进一步升高;锰染毒和染毒后治疗组的5-羟色胺(5-HT)及5-羟吲哚醋酸(5-HIAA)的变化与DA相似,但PAS-Na使5-HT、5-HIAA水平升高的幅度大都较NE和DA的要小,提示5-HT能神经元对PAS-Na治疗作用的敏感性低于儿茶酚胺(CA)能神经元。     

刺五加苷E对小鼠学习及记忆能力的影响

目的探讨刺五加苷E对对氯苯丙氨酸(PCPA)造模小鼠学习记忆行为以及对海马内单胺类神经递质5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NA)的影响。方法 Balb/c小鼠随机分为空白组,模型组,阳性药组,刺五加苷E(ELE)高、中、低剂量组。以PCPA腹腔注射建立小鼠损伤模型,给药14d后Morris水迷宫实验测试小鼠的学习记忆能力,Elisa试剂盒测定小鼠海马组织中5-HT、5-HIAA、DA、NA的含量。结果行为学结果显示,模型组小鼠穿越平台次数较空白组明显降低(P<0.01),ELE高、中剂量组可明显增加小鼠穿越平台次数(P<0.01),模型组小鼠5-HT、5-HIAA较空白组显著降低(P<0.01),NA也显著降低(P<0.05)。ELE各剂量组5-HT、5-HIAA含量较模型组显著升高(P<0.01或P<0.05),ELE高、中剂量可明显改善DA、NA的含量,且与模型组相比,差异显著(P<0.01或P<0.05)。结论ELE提高PCPA造模小鼠学习记忆能力可能与其改善海马组织中5-HT、5-HIAA、DA和NA的含量有关。     

瑞香素与中枢单胺类介质的关系

本文报道从中草药祖师麻中提得的单一成分瑞香素(7,8-二羟基香豆素),也曾称为祖师麻甲素。其镇痛作用能被5-羟色胺(5-HT)和去甲肾上腺素(NA)所加强,同时本实验室测定了在药物作用的峰值时间几个脑区的单胺类介质(5-HT,NA,DA)及代谢物(5-HIAA)的含量,结果显示药物使“低位脑干”(包括中脑、桥脑和延脑)部位的5-HIAA含量显著增加(+133.3%),而对其它脑区及介质均无明显作用。     

瑞香素与中枢单胺类介质的关系

本文报道从中草药祖师麻中提得的单一成分瑞香素(7,8-二羟基香豆素),也曾称为祖师麻甲素。其镇痛作用能被5-羟色胺(5-HT)和去甲肾上腺素(NA)所加强,同时本实验室测定了在药物作用的峰值时间几个脑区的单胺类介质(5-HT,NA,DA)及代谢物(5-HIAA)的含量,结果显示药物使“低位脑干”(包括中脑、桥脑和延脑)部位的5-HIAA含量显著增加(+133.3%),而对其它脑区及介质均无明显作用。     

头面部针刺镇痛与中枢神经递质的关系 毁损大白鼠中脑中缝核群对针刺镇痛的影响

在针麻原理的研究中,针刺镇痛与中枢神经递质的关系日益受到重视。根据现有资料,针刺镇痛与中枢5-羟色胺、去甲肾上腺素、多巴胺和乙酰胆碱等多种神经递质都有关系。其中与脑内5-羟色胺能系统的关系尤为密切。总的来说,在针刺镇痛过程中,脑内5-羟色胺(5-HT)及其代谢产物5-羟吲哚乙酸(5HIAA)含量有所升高。用生理学或药理学方法降低5-羟色胺能系统的功能,可减弱针刺镇痛效应,相反,用生理学或药理学方法,加强5-羟色胺能系统的功能,则增强针刺镇痛效应。     

白松片对慢性应激大鼠海马单胺类神经递质含量的影响

目的:观察中药白松片对应激大鼠海马单胺类神经递质含量的影响。方法:健康成年雄性SD大鼠42只,随机分为正常对照组、模型对照组、氟西汀对照组(1.8mg·kg-1)及白松片3个剂量(4.32,13.0,21.6g·kg-1,生药量)组。每只大鼠每日灌胃给药1次,连续14d。给药d6始,通过强迫游泳建立应激大鼠模型。用高效液相色谱-电化学法测定大鼠海马单胺类神经递质及其代谢产物的含量。结果:模型对照组大鼠海马去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)含量及多巴胺/3,4-二羟苯乙酸(DA/DOPAC)和5-羟色胺/5-羟吲哚乙酸(5-HT/5-HIAA)的比值分别为(4.7±s1.3)nmol·g-1,(47±12)nmol·g-1,(0.97±0.22)nmol·g-1,19±4,0.23±0.06,低于正常对照组(P<0.05或P<0.01);NE/5-HT比值(4.9±0.9)高于正常对照组(P<0.01);用白松片预防给药可使模型大鼠海马NE,DA和5-HT含量及NE/5HT,DA/DOPAC和5-HT/5-HIAA的比值恢复至正常水平(P<0.05或P<0.01)。结论:白松片可能通过提高NE,DA及5-HT的含量并降低其代谢率来发挥其抗抑郁作用。     

吡喹酮对大鼠单胺介质的影响

吡喹酮是一种新型广谱抗寄生虫药。本文报道用高效液相色谱-电化学检测器联用的方法,测定单胺类神经介质及其代谢物的含量,研究吡喹酮对大鼠单胺类介质的影响。结果表明:吡喹酮(250 mg/kg使脑DA的酸性代谢产物DOPAC,HVA和5-HT的代谢物5-HIAA的含量明显升高,而对DA和NA含量无明显影响。DA酸性代谢物和5-HIAA升高表明吡喹酮能增加DA和5-HT的转换率。     

The effect of antidepressants on aversive periaqueductal gray stimulation in rats

The selective serotonin (5-HT) uptake inhibitors fluvoxamine and sertraline had anti-aversive effects when administered acutely. Imipramine and clomipramine, which combine noradrenaline (NA) and 5-HT uptake blocking properties, did not have significant effects, whereas the mixed dopamine (DA)/NA uptake blocker nomifensine decreased the thresholds for escape from aversive periaqueductal gray stimulation. These results suggest that indirect 5-HT receptor activation suppresses periaqueductal gray aversion. Conversely, indirect DA and perhaps NA receptor activation appears to enhance periaqueductal gray aversion in rats.     

Effects of acute ethanol administration on monoamine and metabolite content in forebrain regions of ethanol-tolerant and -nontolerant alcohol-preferring (P) rats

The contents of dopamine (DA), serotonin (5-HT) and their metabolites in the frontal cortex, anterior striatum, nucleus accumbens and hypothalamus of alcohol-tolerant and -nontolerant rats of the alcohol-preferring P line were determined one hour after the IP administration of 2.5 g ethanol/kg body wt. Compared with saline-injected controls, nontolerant P-rats injected with ethanol had (a) 60% higher levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the frontal cortex; (b) 30-60% higher levels of DOPAC and HVA in the anterior striatum and nucleus accumbens; and (c) 20% higher levels of 5-HIAA in all three forebrain regions. In the tolerant group, the effects of IP ethanol on DOPAC and HVA were markedly attenuated or completely eliminated in these three forebrain regions. However, in the case of 5-HIAA, an attenuated response was observed only in the nucleus accumbens of the tolerant group. The IP administration of ethanol had little effect on the contents of DA or 5-HT in any of these three forebrain regions, with the exception that 5-HT levels were elevated in the anterior striatum of both the tolerant and nontolerant groups. In the hypothalamus, there were no significant differences for the contents of DA, 5-HT or their metabolites between the nontolerant or tolerant P rats after IP ethanol. The data indicate that both acute ethanol administration and chronic alcohol intake by the P line of rats alters certain DA and 5-HT systems that may be involved in the brain reward circuitry and in DA pathways involved in motor functions.     

Microdialysis studies on 3,4-methylenedioxyamphetamine and structurally related analogues.

The acute effect of 3,4-methylenedioxyamphetamine (MDA) and three structural analogues on the extracellular concentrations of dopamine (DA) and its major metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum was studied using in vivo microdialysis in awake, freely moving rats. MDA significantly (P less than 0.001) increased and decreased the extracellular concentrations of DA and its metabolites, respectively, following i.p. administration. Similarly, acute administration of the N-methyl (MDMA) and N-ethyl (MDE) derivatives of MDA significantly (P less than 0.05) increased the concentration of DA in the striatum. The alpha-ethyl homologue of MDMA, MBDB, increased the extracellular concentration of DA but significantly (P less than 0.05) less than MDA, MDMA, or MDE. The rank order of potency for these amphetamine derivatives to increase the extracellular concentration of DA was: MDA greater than MDMA greater than MDE greater than MBDB greater than vehicle. The increase in extracellular DA concentration following a single administration of these compounds was negatively correlated with the level of serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the contralateral striatum measured 7 days following drug administration. Thus, extending the alkyl group on the nitrogen or alpha-carbon of MDA reduces the ability of these compounds both to increase acutely the extracellular concentration of DA and to produce long-lasting depletions of 5-HT in the brain.     

5-Hydroxytryptamine and antinociception

The considerable evidence supporting a role for 5-hydroxytryptamine (5-HT) in the modulation of nociceptive thresholds is reviewed. The postulate that an antinociceptive system of neurones projects from periaqueductal gray (PAG) to nucleus raphe magnus (NRM) and then to the dorsal horn, via cells containing 5-HT, has proved difficult to support experimentally. 5-Hydroxytryptamine, applied iontophoretically to dorsal horn neurones, does reduce the nociceptive responses of these neurones but it is not clear that activity in 5-HT cells of the raphe-spinal system is responsible for the descending inhibition of nociception. Although antagonists of 5-HT block some of the antinociceptive effects of both stimulation of the periaqueductal gray and systemically-applied morphine, they do not block the centrifugal inhibition of dorsal horn cells or the effects of iontophoretically applied 5-HT. Nor do they displace [³H]5-HT binding at low concentrations. Damage to, or selective depletion of 5-HT from the raphe-spinal 5-HT system has been reported not to alter nociceptive thresholds or the effects of stimulation of the periaqueductal gray.There is anatomical evidence for cells in the periaqueductal gray which contain 5-HT and project to the n. raphe magnus. Microinjected into the n. raphe magnus, 5-HT is antinociceptive in the tail-flick test and microinjection of an inhibitor of uptake of 5-HT or a 5-HT releasing agent, both cause antinociception. Furthermore, the effects of electrical stimulation of the periaqueductal gray are blocked by microinjection of a 5-HT antagonist into the n. raphe magnus. These observations suggest that 5-HT possibly mediates antinociceptive neurotransmission between the periaqueductal gray and the n. raphe magnus but its role in the dorsal horn is less clear.     

Treatment enhances ultradian rhythms of CSF monoamine metabolites in patients with major depressive episodes.

Unipolar and bipolar depressions show abnormal behavioral manifestations of ultradian (less than 24 h) rhythms, but abnormal rhythms of the central neurotransmitters thought to be important for depression pathophysiology (eg dopamine (DA) and serotonin (5-HT)) have not been shown in this time frame. Since antidepressant treatments normalize disrupted rhythms in depression (eg rapid-eye-movement sleep and hormonal rhythms), we hypothesized that depression-related changes in ultradian oscillations of DA and 5-HT might be revealed during antidepressant treatment. Cerebrospinal fluid (CSF) samples collected q10 min for 24 h in 13 patients experiencing major depressive episodes (MDE) before and after treatment for 5 weeks with sertraline or bupropion were assayed for levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), and their ratio was calculated. Data were analyzed in the frequency domain using Fourier transforms and multivariate permutation testing. Antidepressant treatments were associated with decreased variance for 5-HIAA, increased variance for HVA, and markedly increased variance for the HVA : 5-HIAA ratio (p<0.05, p<0.02, and p<0.003, respectively). With treatment, the correlations between 5-HIAA and HVA weakened (p=0.06). Power spectral density (PSD-the Fourier magnitude squared) of the 5-HIAA signals at periods of 1.75 and 3.7 h (both p<0.05) decreased, while circadian cycling of HVA levels (p<0.05) and of the ratio (p<0.005) increased after treatment. The PSD of the full-length HVA : 5-HIAA ratio series after treatment increased in rapid variability (20-103 min periods, p<0.05). Spectrographic windowing demonstrated a focal span of enhanced HVA : 5-HIAA ratio variability following antidepressant treatment, in an approximately 84-min period through the evening (p<0.05). Periodic neurotransmitter relationships in depressed patients were altered by treatment in this analysis of a small data set. This may represent a baseline abnormality in the regulation of periodic functions involved in the depression pathophysiology, but it could also be due to an unrelated antidepressant effect. Further studies including comparisons with healthy subject data are in progress.     

Increased dopaminergic and 5-hydroxytryptaminergic activities in male rat brain following long-term treatment with anabolic androgenic steroids

1. The effects of treating groups of rats with four different anabolic androgenic steroids (AAS) (testosterone, nandrolone, methandrostenolone, and oxymetholone) on 5-hydroxytryptamine (5-HT) and dopamine (DA) neurones in different brain regions were examined. The AAS was injected six times with 1 week's interval and the rats were sacrificed 2 days after the final injection. 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured. The effect on DA and 5-HT synthesis rate was analysed as the accumulation of 3,4-dihydroxyphenyl-alanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of the amino acid decarboxylase with NSD-1015 (3-hydroxy-benzylhydrazine dihydrochloride). Additionally, the monoamine oxidase (MAO) activity was analysed in the hypothalamus. 2. The DOPAC + HVA/DA ratio was increased in the striatum in all treatment groups. However, the synthesis rate of DA was significantly increased only in the methandrostenolone treated group. 3. The 5-HIAA/5-HT ratio was increased in all treatment groups in the hippocampus, in the frontal cortex in the methandrostenolone-treated animals and in the hypothalamus in the testosterone- and oxymetholone-treated rats, while the 5-HT synthesis rate was not affected by the AAS-treatments. 4. The MAO-A activity was increased in the oxymetholone-treated rats while the other treatment groups were unaffected. The MAO-B activity was not changed. 5. The results indicate that relatively high doses of AAS increase dopaminergic and 5-hydroxytryptaminergic metabolism in male rat brain, probably due to enhanced turnover in these monaminergic systems.     

Direct correlation between level of morphine and its biochemical effect on monoamine systems in mouse brain. Evidence for involvement of dopaminergic neurons in the pharmacological action of acute morphine

The pharmacokinetics (uptake and elimination) and pharmacodynamics (biochemical effects on monoamine systems) of morphine in the CNS were investigated concurrently. ICR mice, weighing about 25 g, were injected intravenously with several doses (2.5-80 mg/kg) of morphine. The animals were killed by microwave irradiation (5 kW, 0.6 sec) at 10 and 30 min, and 1, 2, 4, 8 and 24 hr after the injection. The intracerebral levels of morphine and metabolically related substances consisting of monoamines [noradrenaline, dopamine (DA), 5-hydroxytryptamine (5-HT), 3, 4-dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylacetic acid [homovanillic acid (HVA)], 5-hydroxyindoleacetic acid (5-HIAA), tyrosine and tryptophan] were determined in identical samples by a combination of organic extraction and high-performance liquid chromatography with electrochemical detection. The intracerebral level of morphine was found to depend on the dose injected, and the biological half-life of the drug was estimated to be about 1 hr. The morphine injection (2.5-80 mg/kg) caused significant increases in monoamine metabolites although only slight changes occurred in the concns of parent transmitters. The intracerebral level of morphine was significantly correlated with the ratios DOPAC/DA and HVA/DA (r = 0.7033, P less than 0.0001; and r = 0.6455, P less than 0.0001, respectively). On the other hand, the correlation between the morphine level and 5-HIAA/5-HT was lower than those for DOPAC/DA and HVA/DA. These results suggest that monoamine systems, especially DA, are closely involved in the biochemical effects of morphine. Furthermore, the proposed procedure is demonstrated to be useful as a new approach in biochemical pharmacology, where the direct correlation between the distribution of a drug (pharmacokinetics) and the biochemical effects of the drug (pharmacodynamics) can be measured.     

Cocaine and regional brain monoamines in mice.

Cocaine HCl (0, 10, or 50 mg/kg) was injected into adult male ICR mice IP. Thirty minutes later, brains were removed and nine regions were isolated: olfactory bulbs (OB), olfactory tubercles (OT), prefrontal cortex (PC), septum (SP), striatum (ST), amygdala (AMY), hypothalamus (HT), hippocampus (HC), and thalamus (TH). Using high-performance liquid chromatography, concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and their major metabolites were determined. At 10 mg/kg cocaine, NE levels were increased in the AMY and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), was decreased in the PC, AMY, and HT. DA levels were also increased in the AMY, while its intracellular metabolite, dihydroxyphenylacetic acid (DOPAC), was decreased in the ST and its extracellular metabolite, homovanillic acid (HVA), was decreased in the PC. 3-Methoxytyramine (3-MT) levels were not altered in any tissue. 5-HT levels were increased in the AMY, HT, and TH, while its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was decreased in the OB and ST. MHPG/NE ratios were decreased in the PC, AMY, and HT as were those for HVA/DA. DOPAC/DA ratios were decreased in the ST and AMY and increased in the SP while those for 3-MT/DA were decreased in the TH and increased in the PC. 5-HIAA/5-HT ratios were decreased in the AMY, HC and TH. At 50 mg/kg cocaine, there was an increase in DA in the TH. There was a decrease in DOPAC, HVA, and 3-MT, as well as the DOPAC/DA ratio in the ST. In the OT, there was a decrease in DOPAC, the DOPAC/DA ratio, 3-MT, and the 3-MT/DA ratio.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations in the metabolism of serotonin and dopamine in the mouse brain following a single administration of allylnitrile, which induces long-term dyskinesia.

The effects of allylnitrile (ALN), which induces a long-term dyskinesia in mice, on the metabolism of serotonin (5-HT) and dopamine (DA) were studied after a single administration. One day after injection, ALN produced a significant increase in the levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA): 5-HT in the brain cortex, medulla oblongata plus pons, hypothalamus and midbrain; 5-HIAA in the cortex, medulla oblongata plus pons, striatum, hypothalamus and midbrain; the ratio of 5-HIAA/5-HT in the medulla oblongata plus pons, striatum and midbrain; HVA in the cortex and midbrain. These changes were not seen 10 and 35 days after injection when the animals were showing behavioral abnormalities. The present findings suggest that changes in 5-HT and DA metabolism are involved in the appearance of the dyskinetic syndrome.