• 【大鼠下丘脑外侧,可卡因和苯丙胺调节的转录本 (CART) 神经元向背侧中缝和/或蓝斑的投射模式。】 复制标题 收藏 收藏
    DOI:10.1016/j.brainres.2012.11.042 复制DOI
    作者列表:Yoon YS,Lee HS
    BACKGROUND & AIMS: :The present study was designed to reveal the projection patterns of lateral hypothalamic (LH), cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe (DR) and/or the locus coeruleus (LC) in the rat. After the injection of Red or Green Retrobeads into the DR or LC, LH sections were immunostained for CART and/or melanin-concentrating hormone (MCH). First, CART-immunoreactive axon terminals formed close appositions to the DR (or LC) neuronal profiles. Second, a subpopulation of CART neurons containing MCH projected to the monoaminergic nuclei; the majority of labeled neurons were observed in the dorsal hypothalamic area, the dorsal part of the posterior hypothalamic area, and the zona incerta. Cells were also observed in the perifornical part of the LH, the dorsomedial hypothalamic nucleus, the peduncular and the magnocellular parts of the LH. Of the total population of DR (or LC)-projecting cells, CART/MCH co-containing neurons were 9.5% ± 1.6% (or 10.8% ± 1.3% for LC). Finally, a subset of CART (or MCH) neurons provided divergent axon collaterals to the DR and the LC. Of the entire CART (or MCH) cell population, 3.9% ± 0.8% (or 5.6% ± 1.0% for MCH) sent axon collaterals to the DR/LC. CART/MCH co-containing neurons projecting to the DR or LC might be involved in the feeding-related regulation of arousal, stress-related responses, and emotional behaviors. Thus, CART (or MCH) cells that send divergent axon collaterals to the DR/LC might have a simultaneous (and possibly more efficient) way to exert their specific influences on the aminergic nuclei.
    背景与目标: : 本研究旨在揭示下丘脑外侧 (LH),可卡因和苯丙胺调节的转录本 (CART) 神经元向大鼠背侧中缝 (DR) 和/或蓝斑 (LC) 的投射模式。将红色或绿色的回珠注射到DR或LC中后,对LH切片进行了CART和/或黑色素浓缩激素 (MCH) 的免疫染色。首先,CART免疫反应性轴突末端与DR (或LC) 神经元谱形成紧密结合。其次,包含MCH的CART神经元亚群投射到单胺能核; 在下丘脑背侧区域,下丘脑后区域的背侧部分和透明带中观察到大多数标记的神经元。在LH的穹顶周围部分,下丘脑背核,LH的足部和大细胞部分也观察到细胞。在DR (或LC) 投射细胞的总数中,CART/MCH共含神经元为9.5% ± 1.6% (LC为10.8% ± 1.3%)。最后,CART (或MCH) 神经元的子集为DR和LC提供了不同的轴突侧支。在整个CART (或MCH) 细胞群中,3.9% ± 0.8% (或5.6% ± 1.0% MCH) 向DR/LC发送轴突侧支。向DR或LC投射的CART/MCH共含神经元可能参与了与喂养相关的唤醒调节,压力相关的反应和情绪行为。因此,向DR/LC发送不同轴突侧支的CART (或MCH) 细胞可能具有同时 (甚至可能更有效) 对氨基能核施加特定影响的方式。
  • 2 Cocaine and oral health. 复制标题 收藏 收藏

    【可卡因和口腔健康。】 复制标题 收藏 收藏
    DOI:10.1038/sj.bdj.2008.244 复制DOI
    作者列表:Brand HS,Gonggrijp S,Blanksma CJ
    BACKGROUND & AIMS: :In the UK almost one million individuals use cocaine on a regular basis, implying that dentists are likely to encounter individuals that use cocaine. Regular use of this drug may have several orofacial effects, such as perforation of the nasal septum and palate, gingival lesions and erosion of tooth surfaces. In addition, recent use of cocaine increases the risk of a medical emergency during dental treatment, especially when epinephrine-containing local anaesthetics or retraction cords are used. Therefore, dental treatment should be postponed for 6 to 24 hours after the use of cocaine.
    背景与目标: : 在英国,几乎有100万个人定期使用可卡因,这意味着牙医很可能会遇到使用可卡因的人。定期使用这种药物可能会产生多种口腔作用,例如鼻中隔和pa穿孔,牙龈病变和牙齿表面侵蚀。此外,最近使用可卡因会增加牙科治疗期间发生医疗紧急情况的风险,尤其是当使用含有肾上腺素的局部麻醉剂或收缩索时。因此,使用可卡因后,牙科治疗应推迟6至24小时。
  • 【Α-1肾上腺素能受体在可卡因致敏过程中调节谷氨酸和GABA神经传递到腹侧被盖层多巴胺神经元上。】 复制标题 收藏 收藏
    DOI:10.3390/ijms21030790 复制DOI
    作者列表:Velasquez-Martinez MC,Santos-Vera B,Velez-Hernandez ME,Vazquez-Torres R,Jimenez-Rivera CA
    BACKGROUND & AIMS: :The ventral tegmental area (VTA) plays an important role in the reward and motivational processes that facilitate the development of drug addiction. Presynaptic α1-AR activation modulates glutamate and Gamma-aminobutyric acid (GABA) release. This work elucidates the role of VTA presynaptic α1-ARs and their modulation on glutamatergic and GABAergic neurotransmission during cocaine sensitization. Excitatory and inhibitory currents (EPSCs and IPSCs) measured by a whole cell voltage clamp show that α1-ARs activation increases EPSCs amplitude after 1 day of cocaine treatment but not after 5 days of cocaine injections. The absence of a pharmacological response to an α1-ARs agonist highlights the desensitization of the receptor after repeated cocaine administration. The desensitization of α1-ARs persists after a 7-day withdrawal period. In contrast, the modulation of α1-ARs on GABA neurotransmission, shown by decreases in IPSCs' amplitude, is not affected by acute or chronic cocaine injections. Taken together, these data suggest that α1-ARs may enhance DA neuronal excitability after repeated cocaine administration through the reduction of GABA inhibition onto VTA dopamine (DA) neurons even in the absence of α1-ARs' function on glutamate release and protein kinase C (PKC) activation. α1-AR modulatory changes in cocaine sensitization increase our knowledge of the role of the noradrenergic system in cocaine addiction and may provide possible avenues for therapeutics.
    背景与目标: : 腹侧被盖区 (VTA) 在促进吸毒成瘾发展的奖励和动机过程中起着重要作用。突触前 α1-AR活化调节谷氨酸和 γ-氨基丁酸 (GABA) 的释放。这项工作阐明了VTA突触前 α1-ARs的作用及其对可卡因敏化过程中谷氨酸能和gaba能神经传递的调节。通过全细胞电压钳测量的兴奋性和抑制性电流 (epsc和IPSCs) 表明,在可卡因治疗1天后,但在可卡因注射5天后,α1-ARs激活会增加epsc的幅度。对 α1-ARs激动剂没有药理反应,这凸显了反复服用可卡因后受体的脱敏。在7天的停药期后,α1-ARs的脱敏作用持续存在。相反,ipscs振幅降低显示的 α1-ARs对GABA神经传递的调节不受急性或慢性可卡因注射的影响。总之,这些数据表明,即使在缺乏 α1-ARs对谷氨酸释放和蛋白的功能的情况下,反复服用可卡因后,α1-ARs也可以通过减少GABA对VTA多巴胺 (DA) 神经元的抑制作用来增强DA神经元的兴奋性。激酶C (PKC) 激活。可卡因敏化中的 α1-AR调节变化增加了我们对去甲肾上腺素能系统在可卡因成瘾中的作用的了解,并可能为治疗提供可能的途径。
  • 【在恒河猴中,根据渐进比率时间表评估的可卡因增强强度的影响。】 复制标题 收藏 收藏
    DOI:10.1097/FBP.0b013e3283123c6c 复制DOI
    作者列表:Martelle JL,Czoty PW,Nader MA
    BACKGROUND & AIMS: :Progressive-ratio (PR) schedules of reinforcement have provided valuable information regarding the reinforcing strength of cocaine and the underlying neurobiological mechanisms. Parametric manipulations, such as altering time-out (TO) values, can affect the shape of the cocaine dose-response curve. Earlier studies have used PR schedules with widely varying parameters, thus complicating comparisons across experiments. This study evaluated the reinforcing strength of cocaine (0.005-0.9 mg/kg) as a function of post-reinforcement TO duration (5, 10, 30, or 60 min) under a PR schedule in rhesus monkeys. Daily sessions ended when 2 h elapsed without an injection; the breakpoint value was defined as the total number of injections. When the TO was 10 min, the relationship between cocaine dose and the number of injections received (i.e. BP) was characterized by an inverted U-shaped curve in all monkeys. Increasing the TO to 30 min resulted in a rightward shift of the ascending limb of the dose-response curve, but did not affect self-administration of higher doses. The number of injections received of a low cocaine dose was not further increased when the TO was shortened to 5 min, nor did increasing the TO to 60 min alter self-administration of the highest tested dose. These results suggest that drug accumulation plays a role in determining the reinforcing strength of low and intermediate cocaine doses under PR schedules. However, the reinforcing strength of higher cocaine doses was unaffected by manipulating TO, suggesting that the BP value is a useful measure of reinforcing strength.
    背景与目标: : 渐进比率 (PR) 增强时间表提供了有关可卡因增强强度和潜在神经生物学机制的有价值的信息。参数操作 (例如更改time-out (至) 值) 会影响可卡因剂量反应曲线的形状。早期的研究使用了参数变化很大的PR时间表,因此使实验之间的比较变得复杂。这项研究评估了恒河猴在PR计划下可卡因 (0.005-0.9 mg/kg) 的增强强度与增强后持续时间 (5、10、30或60分钟) 的函数。当2小时过去了而没有注射时,每日疗程结束; 断点值定义为注射总数。当至10分钟时,可卡因剂量与接受的注射次数 (即BP) 之间的关系的特征是所有猴子的U形曲线。增加到30分钟会导致剂量反应曲线的上升肢向右移动,但不会影响较高剂量的自我给药。当将剂量缩短至5分钟时,接受低可卡因剂量的注射次数没有进一步增加,将剂量增加至60分钟也没有改变最高测试剂量的自我给药。这些结果表明,药物积累在确定PR计划下中低可卡因剂量的增强强度中起作用。然而,较高可卡因剂量的增强强度不会受到操纵的影响,这表明BP值是增强强度的有用度量。
  • 【竞争性NMDA受体拮抗剂CPP破坏了可卡因诱导的条件性位置偏好,但避免了行为敏化。】 复制标题 收藏 收藏
    DOI:10.1016/j.bbr.2012.10.042 复制DOI
    作者列表:Carmack SA,Kim JS,Sage JR,Thomas AW,Skillicorn KN,Anagnostaras SG
    BACKGROUND & AIMS: :Recently, the notion that memory and addiction share similar neural substrates has become widely accepted. N-methyl-d-aspartate receptors (NMDAR) are the cornerstones of synaptic models of memory. The present study examined the effect of the competitive NMDAR antagonist CPP on the induction of behavioral sensitization and conditioned place preference to cocaine. Conditioned place preference is an associative memory model of drug seeking, while sensitization is a non-associative model of the transition from casual to compulsive use. There were three principal findings: (1) co-administration of CPP and cocaine altered the acute response to cocaine, suggesting a direct interaction between the two drugs; (2) NMDAR antagonism had no effect on behavioral sensitization; and (3) NMDAR antagonism abolished conditioned place preference. A review of prior evidence supporting a role for NMDARs in sensitization suggests that NMDAR antagonists directly interfere with cocaine's psychostimulant effects, and this interaction could be misinterpreted as a disruption of sensitization. Finally, we suggest that addiction recruits multiple kinds of plasticity, with sensitization recruiting NMDAR-independent mechanisms.
    背景与目标: : 最近,记忆和成瘾共享相似神经底物的观念已被广泛接受。N-甲基-d-天冬氨酸受体 (NMDAR) 是记忆突触模型的基石。本研究检查了竞争性NMDAR拮抗剂CPP对可卡因的行为敏化和条件性位置偏好的诱导作用。条件性场所偏好是寻求药物的联想记忆模型,而敏化是从随意使用到强迫使用的非联想模型。有三个主要发现 :( 1) CPP和可卡因的共同给药改变了对可卡因的急性反应,表明两种药物之间存在直接相互作用; (2) NMDAR拮抗作用对行为敏化没有影响; (3) NMDAR拮抗作用消除了条件性位置偏好。对支持NMDARs在致敏作用中的先前证据的审查表明,NMDAR拮抗剂直接干扰可卡因的精神刺激作用,这种相互作用可能被误解为致敏的破坏。最后,我们建议成瘾招募多种可塑性,并通过敏感性招募与NMDAR无关的机制。
  • 【验证了心包液中可卡因和代谢物的气相色谱-质谱分析程序。】 复制标题 收藏 收藏
    DOI:10.1093/jat/31.2.75 复制DOI
    作者列表:Contreras MT,González M,González S,Ventura R,Valverde JL,Hernández AF,Pla A,Vingut A,Segura J,de la Torre R
    BACKGROUND & AIMS: :A method is described for the simultaneous quantification of cocaine, benzoylecgonine, and cocaethylene in pericardial fluid. Pericardial fluid samples from autopsy casework involving cocaine-related deaths and deaths unrelated to drug abuse were collected. The extraction of cocaine and its metabolites was performed using Bond-Elut Certify columns. Pericardial fluid samples were adjusted to pH 7 and applied to the pre-conditioned cartridges. After the washing steps, compounds were eluted with a mixture of chloroform/isopropanol (80:20) with 2% ammonium hydroxide. The dry extracts were derivatized with pentafluoropropionic anhydride and hexafluoroisopropanol and analyzed by gas chromatography-mass spectrometry using electron impact ionization and selective ion monitoring acquisition. Deuterated internal standards were used. The analytical method developed was linear, sensitive, selective, accurate, and sufficiently precise to be applied routinely in forensic toxicology. In this study, the procedure has been successfully applied to a number of forensic cases involving cocaine intoxication.
    背景与目标: : 描述了一种同时定量心包液中可卡因,苯甲酰芽甘氨酸和可卡因乙烯的方法。收集了来自涉及可卡因相关死亡和与药物滥用无关的死亡的尸检案例的心包液样本。可卡因及其代谢物的提取是使用Bond-Elut认证柱进行的。将心包液样品调节至pH 7,并应用于预处理的药筒。在洗涤步骤之后,用氯仿/异丙醇 (80 ∶ 20) 与2% 氢氧化铵的混合物洗脱化合物。将干提取物用五氟丙酸酐和六氟异丙醇衍生化,并通过电子碰撞电离和选择性离子监测采集的气相色谱-质谱法进行分析。使用了氘代内部标准。开发的分析方法是线性的,灵敏的,选择性的,准确的,并且足够精确,可以在法医毒理学中常规应用。在这项研究中,该程序已成功应用于许多涉及可卡因中毒的法医案件。
  • 【在帕金森综合征模型小鼠中,可卡因诱导的CREB磷酸化和c-Fos表达受到抑制。】 复制标题 收藏 收藏
    DOI:10.1097/00001756-199511000-00023 复制DOI
    作者列表:Kano T,Suzuki Y,Shibuya M,Kiuchi K,Hagiwara M
    BACKGROUND & AIMS: :Cocaine exerts multiple neurochemical effects in the central nervous system through inhibition of the dopamine transporter at the synapse. Here we report that systemic administration of the drug induces rapid phosphorylation of CREB in the mouse striatum where expression of the nuclear proto-oncogene c-fos is observed. In MPTP-treated mice, in which dopaminergic neurones are degenerated and which show Parkinsonism-like behaviour, however, CREB phosphorylation is not induced by cocaine exposure and c-fos expression is significantly depressed in comparison with controls. These data suggest that CREB may play a major role in the dopaminergic activation of c-fos in the striatum and that the lack of a CREB-induced transcription cascade may have a critical relevance for long-lasting psychomotor disorders in Parkinsonism.
    背景与目标: : 可卡因通过抑制突触中的多巴胺转运蛋白在中枢神经系统中发挥多种神经化学作用。在这里,我们报告了药物的全身给药诱导小鼠纹状体中CREB的快速磷酸化,其中观察到核原癌基因c-fos的表达。在MPTP处理的小鼠中,多巴胺能神经元退化并显示出类似帕金森病的行为,但是,可卡因暴露不会诱导CREB磷酸化,并且与对照组相比,c-fos表达显着降低。这些数据表明,CREB可能在纹状体中c-fos的多巴胺能激活中起主要作用,并且缺乏CREB诱导的转录级联反应可能与帕金森氏症的长期精神运动障碍具有关键意义。
  • 【多巴胺能和谷氨酸能受体拮抗剂对大鼠可卡因条件运动的建立和表达的影响。】 复制标题 收藏 收藏
    DOI:10.1016/0006-8993(96)00455-6 复制DOI
    作者列表:Cervo L,Samanin R
    BACKGROUND & AIMS: A series of experiments were conducted to investigate the role of dopaminergic D1 and D2 and glutamatergic NMDA and AMPA/kainate receptors on the establishment and expression of cocaine-induced conditioned locomotion in rats. In the first experiment conditioned locomotion was demonstrated by testing the animals in an environment previously associated with 15 mg/kg i.p. cocaine. The D2-receptor antagonist (-)-sulpiride (50 and 100 mg/kg i.p.) administered before cocaine during the conditioning phase did not modify the establishment of conditioned locomotion whereas when administered before testing only at the higher dose it partially reduced rats' locomotion in the absence of cocaine (expression). At the higher dose (0.1 mg/kg i.p.) the D1-receptor antagonist SCH 23390 attenuated the expression of cocaine-induced conditioned locomotion whereas the lower dose (0.03 mg/kg i.p.) had no effect. Both doses of the NMDA receptor antagonist MK-801 (0.125 and 0.25 mg/kg i.p.) blocked the development of cocaine-induced conditioned locomotion but neither dose, when administered before testing, modified locomotion in the absence of cocaine. Both doses of the AMPA/kainate receptor antagonist DNQX administered intracerebroventricularly (1 and 3 micrograms/rat) blocked cocaine-induced conditioned locomotion when given before cocaine during conditioning but when given before testing only the higher dose attenuated the conditioned activity. The results confirm the importance of the interaction between glutamatergic and dopaminergic systems for the conditional factors maintaining drug seeking behaviour. The findings may have implications for the treatment of cocaine craving and relapse.

    背景与目标: 进行了一系列实验,以研究多巴胺能D1和D2以及谷氨酸能NMDA和AMPA/kainate受体在可卡因诱导的条件性运动的建立和表达中的作用。在第一个实验中,通过在先前与15 mg/kg i.p.可卡因相关的环境中测试动物,证明了条件性运动。在调节阶段期间在可卡因之前施用的D2-receptor拮抗剂 (-)-舒必利 (50和100 mg/kg i.p.) 不改变条件运动的建立,而当仅以较高剂量在测试之前施用时,在不存在可卡因 (表达) 的情况下部分减少了大鼠的运动。在较高剂量 (0.1 mg/kg i.p.) 下,D1-receptor拮抗剂SCH 23390减弱可卡因诱导的条件性运动的表达,而较低剂量 (0.03 mg/kg i.p.) 则没有作用。两种剂量的NMDA受体拮抗剂MK-801 (0.125和0.25 mg/kg i.p.) 均阻断可卡因诱导的条件性运动的发展,但在测试前给药时,两种剂量均未在不存在可卡因的情况下改变运动。两种剂量的AMPA/kainate受体拮抗剂DNQX在脑室内给药 (1和3微克/大鼠) 时,在可卡因调理期间给予可卡因诱导的条件性运动,但在测试前给予时,仅较高剂量会减弱条件性活性。结果证实了谷氨酸能和多巴胺能系统之间相互作用对于维持药物寻求行为的条件因素的重要性。这些发现可能对可卡因渴望和复发的治疗有影响。
  • 【在门诊治疗和1年的随访中,临时加强会增加可卡因的戒断。】 复制标题 收藏 收藏
    DOI:10.1037//0022-006x.68.1.64 复制DOI
    作者列表:Higgins ST,Wong CJ,Badger GJ,Ogden DE,Dantona RL
    BACKGROUND & AIMS: :This study assessed whether contingent incentives can be used to reinforce cocaine abstinence in dependent outpatients. Seventy cocaine-dependent outpatients were randomized into 2 conditions. All participants received 24 weeks of treatment and 1 year of follow-up. The treatment provided to all participants combined counseling based on the community reinforcement approach with incentives in the form of vouchers exchangeable for retail items. In 1 condition, incentives were delivered contingent on cocaine-free urinalysis results, whereas in the other condition incentives were delivered independent of urinalysis results. Abstinence-contingent incentives significantly increased cocaine abstinence during treatment and 1 year of follow-up compared with noncontingent incentives.
    背景与目标: : 这项研究评估了是否可以使用或有激励措施来加强依赖门诊患者的可卡因戒断。70名可卡因依赖型门诊患者被随机分为2种情况。所有参与者均接受了24周的治疗和1年的随访。向所有参与者提供的治疗将基于社区强化方法的咨询与可兑换零售商品的优惠券形式的激励措施相结合。在1种情况下,激励措施取决于无可卡因的尿液分析结果,而在其他情况下,激励措施与尿液分析结果无关。与非偶然诱因相比,禁欲或有诱因可显着增加治疗期间和随访1年的可卡因禁欲。
  • 【东pol碱的内侧前额叶皮质注射可增加可卡因的仪器反应: 大鼠静脉内自我给药研究。】 复制标题 收藏 收藏
    DOI:10.1016/s0361-9230(99)00214-2 复制DOI
    作者列表:Ikemoto S,Goeders NE
    BACKGROUND & AIMS: :The present experiments examined the effects of muscarinic cholinergic receptor blockade in the nucleus accumbens (NAC) and medial prefrontal cortex (MPC) on intravenous cocaine self-administration. Adult male Sprague-Dawley rats were implanted with chronic indwelling jugular catheters and guide cannulae stereotaxically aimed at the NAC or MPC. The rats were then given the opportunity to intravenously self-administer cocaine (0.8 mg/kg/infusion) during daily 2-h sessions. Intra-NAC microinjections of methyl-scopolamine (2, 4, 8, 16, and 32 microg/side) or vehicle did not affect either the number of lever presses made or infusions delivered. On the other hand, intra-MPC injections of scopolamine significantly increased responding, although there was only a trend for an increase in the number of cocaine infusions. The effects of intra-MPC injections of scopolamine (8 and 16 microg/side) on locomotor activity were also evaluated. Intra-MPC injections of scopolamine (16 microg/side) produced significant increases in locomotor activity. However, these same microinjections decreased locomotor activity when the animals also received cocaine (15 mg/kg, i.p.). These results suggest that cholinergic neurotransmission at muscarinic receptors in the MPC is involved in regulating cocaine-maintained responding.
    背景与目标: : 本实验研究了伏隔核 (NAC) 和内侧前额叶皮层 (MPC) 中毒蕈碱胆碱能受体阻滞对静脉内可卡因自我给药的影响。将成年雄性Sprague-Dawley大鼠植入慢性留置的颈静脉导管,并以立体定向的方式引导套管,以NAC或MPC为目标。然后给大鼠在每天2小时的时间内静脉内自我施用可卡因 (0.8 mg/kg/输注) 的机会。NAC内部微注射甲基东莨菪碱 (2、4、8、16和32微克/侧) 或媒介物不会影响所制造的杠杆压机或输注的数量。另一方面,尽管只有可卡因输注数量增加的趋势,但MPC内注射东pol碱显着增加了反应。还评估了MPC内注射东莨菪碱 (8和16微克/侧) 对运动活性的影响。MPC内注射东pol碱 (16微克/侧) 可显着增加运动活性。但是,当动物也接受可卡因 (15 mg/kg,ip) 时,这些相同的微注射会降低运动活性。这些结果表明,MPC中毒蕈碱受体的胆碱能神经传递参与调节可卡因维持的反应。
  • 【重复服用苯丙胺和可卡因对大鼠血浆中肾上腺,性腺和甲状腺激素水平的影响。】 复制标题 收藏 收藏
    DOI:10.1055/s-0029-1211463 复制DOI
    作者列表:Budziszewska B,Jaworska-Feil L,Lasoń W
    BACKGROUND & AIMS: Effects of acute and repeated administration of cocaine and amphetamine on adrenal, gonadal and thyroid plasma hormone levels were studied in male rats. Acute and repeated cocaine (15 mg/kg i.p. one dose, or once an hour for 3 hr for 8 days) enhanced the corticosterone level at 45 min after administration. Amphetamine (5 mg/kg i.p. one dose, or twice daily for 14 days) elevated the level of corticosterone after 2 hr. Acute amphetamine increased the progesterone, testosterone and androstenedione plasma levels, whereas acute cocaine had no effect on those parameters. Repeated psycho-stimulants decreased the level of androgens. Neither acute nor repeated administration of psychostimulants had any significant effect on the level of the thyroid hormone T3. The T4 plasma level decreased following repeated amphetamine only. The above results indicate that repeated psychostimulants enhance the activity of the hypothalamo-pituitary-adrenal (HPA) axis and lead to a decrease in the hypothalamo-pituitary-gonadal (HPG) axis activity. On the other hand, the hypothalamo-pituitary-thyroid (HPT) axis seems to be more resistant to the psychostimulant action.

    背景与目标: 在雄性大鼠中研究了可卡因和苯丙胺的急性和反复给药对肾上腺,性腺和甲状腺血浆激素水平的影响。急性和重复可卡因 (15 mg/kg i.p.一剂,或每小时一次,持续3小时,持续8天) 在给药后45分钟提高了皮质酮水平。苯丙胺 (5 mg/kg i.p.一剂,或每天两次,持续14天) 在2小时后升高皮质酮水平。急性苯丙胺增加了孕酮,睾丸激素和雄烯二酮的血浆水平,而急性可卡因对这些参数没有影响。反复的心理兴奋剂降低了雄激素的水平。急性或反复给药精神刺激剂对甲状腺激素t3水平没有任何显着影响。仅重复苯丙胺后,T4血浆水平降低。以上结果表明,反复的精神刺激剂会增强下丘脑-垂体-肾上腺 (HPA) 轴的活性,并导致下丘脑-垂体-性腺 (HPG) 轴的活性降低。另一方面,下丘脑-垂体-甲状腺 (HPT) 轴似乎对精神刺激作用更具抵抗力。
  • 【雌二醇增强对可卡因和苯丙胺刺激的纹状体 [3H] 多巴胺释放的行为敏感性。】 复制标题 收藏 收藏
    DOI:10.1016/0006-8993(91)91706-7 复制DOI
    作者列表:Peris J,Decambre N,Coleman-Hardee ML,Simpkins JW
    BACKGROUND & AIMS: :Locomotor activity and stereotypy induced by cocaine is increased or 'sensitized' after repeated cocaine administration. This behavioral sensitization may be mediated by a persistent increase in dopamine (DA) transmission in mesolimbic and nigrostriatal pathways. Since the female estrous cycle and ovarian steroid hormones appear to affect both cocaine sensitization and DA transmission, studies were undertaken to determine the effects of ovarian steroids on sensitization of the behavioral responses to repeated cocaine injections and any concomitant effects on striatal DA release. Young female adult rats were ovariectomized and 2 weeks later were implanted with chronic release forms of estradiol (E), progesterone (P), both (EP) or vehicle (V). Locomotor and stereotypic behavior were rated after an initial injection of either saline or cocaine (10 mg/kg, i.p.) and after the 8th daily injection of saline or cocaine. A significant increase in both locomotor and stereotypic behaviors was seen after the first cocaine injection relative to saline-injected animals and this response was not affected by steroid treatment. Repeated injections of cocaine caused sensitization of the initial behavioral response to cocaine (i.e. an increase in stereotypic and locomotor behavior) and the degree of cocaine sensitization was greatest in group E. Steroid treatment did not affect behavior in saline-treated rats. When striatal [3H]DA release was measured in vitro 1 or 7 days after the last injection, amphetamine-stimulated release was greater in vehicle-treated rats 7 days after cocaine injections but not 1 day after injections. In contrast, release was enhanced in group E both 1 and 7 days after cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)
    背景与目标: : 可卡因诱导的运动活性和刻板印象在反复服用可卡因后增加或 “敏感”。这种行为敏化可能是由中脑边缘和黑质纹状体途径中多巴胺 (DA) 传递的持续增加介导的。由于女性发情周期和卵巢类固醇激素似乎同时影响可卡因致敏和DA传递,因此进行了研究以确定卵巢类固醇对反复注射可卡因的行为反应的致敏作用以及对纹状体DA释放的任何伴随影响。将年轻的成年雌性大鼠卵巢切除,并在2周后植入雌二醇 (E),孕酮 (P),两者 (EP) 或赋形剂 (V) 的慢性释放形式。在初次注射盐水或可卡因 (10 mg/kg,i.p.) 和第8次每日注射盐水或可卡因后,对运动和定型行为进行了评估。相对于注射盐水的动物,第一次注射可卡因后,运动和刻板行为均显着增加,并且这种反应不受类固醇治疗的影响。反复注射可卡因会导致对可卡因的初始行为反应敏感 (即刻板印象和运动行为的增加),而e组的可卡因敏感程度最大。类固醇治疗不会影响盐水治疗大鼠的行为。当在最后一次注射后1或7天体外测量纹状体 [3H]DA释放时,可卡因注射后7天,但注射后1天,在媒介物治疗的大鼠中,苯丙胺刺激的释放更大。相反,E组在可卡因后1天和7天释放均增强。(摘要截短于250个单词)
  • 【[35岁男性静脉注射可卡因后出现腰痛发热]。】 复制标题 收藏 收藏
    DOI:10.1157/13093476 复制DOI
    作者列表:Fernández Jiménez P,Sáez Méndez L,Solera Santos J
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【1990-2000年纽约市可卡因和鸦片相关的致命过量。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2458-7-31 复制DOI
    作者列表:Bernstein KT,Bucciarelli A,Piper TM,Gross C,Tardiff K,Galea S
    BACKGROUND & AIMS: BACKGROUND:In New York City (NYC), the annual mortality rate is higher for accidental drug overdoses than for homicides; cocaine and opiates are the drugs most frequently associated with drug overdose deaths. We assessed trends and correlates of cocaine- and opiate-related overdose deaths in NYC during 1990-2000. METHODS:Data were collected from the NYC Office of the Chief Medical Examiner (OCME) on all fatal drug overdoses involving cocaine and/or opiates that occurred between 1990-2000 (n = 8,774) and classified into three mutually exclusive groups (cocaine only; opiates-only; cocaine and opiates). Risk factors for accidental overdose were examined in the three groups and compared using multinomial logistic regression. RESULTS:Overall, among decedents ages 15-64, 2,392 (27.3%) were attributed to cocaine only and 2,825 (32.2%) were attributed to opiates-only. During the interval studied, the percentage of drug overdose deaths attributed to cocaine only fell from 29.2% to 23.6% while the percentage of overdose deaths attributed to opiates-only rose from 30.6% to 40.1%. Compared to New Yorkers who fatally overdosed from opiates-only, fatal overdose attributed to cocaine-only was associated with being male (OR = 0.71, 95% CI 0.62-0.82), Black (OR = 4.73, 95% CI 4.08-5.49) or Hispanic (OR = 1.51, 95% CI 1.29-1.76), an overdose outside of a residence or building (OR = 1.34, 95% CI 1.06-1.68), having alcohol detected at autopsy (OR = 0.50, 95% CI 0.44-0.56) and older age (55-64) (OR = 2.53 95% CI 1.70-3.75)). CONCLUSION:As interventions to prevent fatal overdose become more targeted and drug specific, understanding the different populations at risk for different drug-related overdoses will become more critical.
    背景与目标:
  • 【一种经过验证的液相色谱-大气压化学电离-串联质谱方法,用于定量人血浆中的可卡因和苯甲酰芽氨酸。】 复制标题 收藏 收藏
    DOI:10.1093/jat/25.7.497 复制DOI
    作者列表:Lin SN,Moody DE,Bigelow GE,Foltz RL
    BACKGROUND & AIMS: :In order to support studies on various medication protocols for the treatment of cocaine abuse, an accurate, precise, and sensitive (2.5 to 750 ng/mL) liquid chromatography-tandem mass spectrometry assay was developed to determine cocaine and benzoylecgonine in human plasma. Cocaine-d3 and benzoylecgonine-d3 were added as internal standards and samples were subjected to solid-phase extraction. Cocaine recovery was 94.4% and benzoylecgonine was 80.3% at 2.5 ng/mL. The selected reaction monitoring of parent ions at m/z 304 and 290 resulted in strong fragments at m/z 182 and 168 for cocaine and benzoylecgonine, respectively. The method was fully validated. The mean measured concentration at the 2.5 ng/mL, the lower limit of quantitation, was within 10.8% of the target and the precision determined at the low (5 ng/mL), medium (50 ng/mL), and high (650 ng/mL) quality controls ranged from 0.9 to 6.2 %CV. Cocaine and benzoylecgonine concentrations in plasma treated with 1% NaF showed changes of less than 10% when maintained at room temperature for up to 7 h and no significant changes when subjected to three freeze-thaw cycles. The concentrations of cocaine and benzoylecgonine remained stable in plasma samples stored at -20 degrees C for up to 11 months. Methanolic stock solutions of both analytes are stable, staying within 2% of the freshly prepared stock solutions, when stored at -20 degrees C for up to 235 days. Both extracted analytes reconstituted in methanolic solutions are stable for up to seven days whether stored at -20 degrees C or at room temperature on the autosampler. The method is rugged, rapid, and robust and has been applied to the batch analysis of more than 700 samples during pharmacokinetic profiling to assess potential interactions between intravenous (i.v.) cocaine challenge and treament medications. Results from three of these subjects receiving 40 mg (i.v.) cocaine demonstrate the utility of the method.
    背景与目标: : 为了支持对治疗可卡因滥用的各种药物方案的研究,开发了一种准确,精确和灵敏 (2.5 750 ng/mL) 的液相色谱-串联质谱测定法,以测定人血浆中的可卡因和苯甲酰芽子碱。加入Cocaine-d3和benzoylecgonine-d3作为内标物,样品进行固相萃取。94.4% 可卡因回收,并以2.5 ng/mL 80.3% 苯甲酰腺嘧啶。在m/z 304和290对母体离子的选定反应监测分别导致可卡因和苯甲酰芽子碱在m/z 182和168处的强片段。该方法得到了充分验证。在2.5 ng/mL (定量下限) 下的平均测量浓度在目标的10.8% 内,并且在低 (5 ng/mL),培养基 (50 ng/mL) 下确定的精密度,高 (650 ng/mL) 质量控制范围为0.9至6.2% CV。当在室温下保持长达7小时时,用1% NaF处理的血浆中的可卡因和苯甲酰芽子碱浓度显示出小于10% 的变化,而当经历三个冻融循环时,没有显着变化。在-20摄氏度下储存的血浆样品中,可卡因和苯甲酰腺嘧啶的浓度保持稳定长达11个月。当在-20摄氏度下储存长达235天时,两种分析物的甲醇储备溶液都是稳定的,保持在新鲜制备的储备溶液的2% 内。在甲醇溶液中重构的两种提取的分析物无论在-20摄氏度下还是在自动进样器上的室温下均稳定长达7天。该方法是坚固的、快速的和稳健的,并且已经应用于在药代动力学分析期间对超过700个样品进行分批分析,以评估静脉内 (静脉内) 可卡因攻击和治疗药物之间的潜在相互作用。其中三名接受40 mg (i.v.) 可卡因的受试者的结果证明了该方法的实用性。

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