Opioid Receptors Regulate the Extinction of Pavlovian Fear Conditioning.

Rats received a single pairing of an auditory conditioned stimulus (CS) with a footshock unconditioned stimulus (US). The fear (freezing) that had accrued to the CS was then extinguished. Injection of naloxone prior to this extinction significantly impaired the development of extinction. This impairment was mediated by opioid receptors in the brain and was not observed when naloxone was injected after extinction training. Finally, an injection of naloxone on test failed to reinstate extinguished responding that had already accrued to the CS. These experiments show that opioid receptors regulate the development, but not the expression, of fear extinction and are discussed with reference to the roles of opioid receptors in US processing, memory, and appetitive motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

纳洛酮对大鼠中重度创伤性脑损伤后细胞免疫功能影响的实验研究

目的：通过观察大鼠创伤性脑损伤（traumatic brain injury,TBI）后纳洛酮治疗前后血浆β-EP、CD4＋、CD8＋和IL-2的动态变化,探讨纳洛酮对大鼠TBI后细胞免疫功能变化的影响及作用机制。方法：采用气体冲击致大鼠中重度脑损伤模型;流式细胞术、RIA、ELISA检测血液中CD4＋、CD8＋、β-EP、IL-2的变化。结果：TBI大鼠经纳洛酮治疗后,血浆中CD4＋和IL-2含量升高,β-EP和CD8＋则降低。大、小剂量纳洛酮治疗在相应时间点比较有显著性差异（P〈0.05）。结论：纳洛酮可通过降低TBI大鼠血浆中β-EP,调节TBI后应激紊乱,竞争性抑制β-EP对免疫细胞受体的作用,从而使CD4＋、CD8＋和IL-2水平趋于正常,恢复免疫平衡,起到治疗与保护作用。     

纳美芬对腹腔镜胆囊切除术患者术后呼吸抑制的拮抗作用

目的：探讨纳美芬对腹腔镜胆囊切除术患者术后呼吸抑制的拮抗作用。方法将110例行腹腔镜胆囊切除术患者根据术后使用拮抗药物的不同分为 A 组和 B 组,每组55例。A 组在手术结束后5 min 静脉推注盐酸纳美芬注射液0．25μg·kg－1,B 组在手术结束后5 min 静脉推注纳洛酮1μg·kg－1。观察2组给予拮抗药前,给予拮抗药后2、10 min,拔管后5 min 收缩压（SBP）、舒张压（DBP）、心率（HR）、平均动脉压（MAP）和血氧饱和度（SpO2）的变化以及给予拮抗药后10 min 呼吸恢复率、拔管时间和不良反应（包括躁动、高血压、心动过速、过敏反应和肺水肿）的情况,并对2组拔管后5 min 意识状况及拔管后30 min 镇痛情况进行评分（分别采用 Ramsay 和VAS 评分）。结果A 组拔管时间为（5．4±0．3）min,B 组拔管时间为（6．1±0．4）min,2组比较差异无统计学意义（P ＞0．05）。2组给予拮抗药后2、10 min 和拔管后5 min 时 SBP、DBP、SpO2比较差异均无统计学意义（均 P ＞0．05）,A 组给予拮抗药后10 min 呼吸恢复率明显高于 B 组（P ＜0．05）,2组拔管后30 min VAS 和拔管后5 min Ramsay 得分比较差异均无统计学意义（均 P ＞0．05）。A 组恶心、躁动、转氨酶升高1例（1．8％）,B 组恶心、躁动、转氨酶升高2例（3．6％）,2组比较差异无统计学意义（P ＞0．05）。结论纳美芬可安全、有效地拮抗腹腔镜胆囊切除术患者术后引起的呼吸抑制,且患者呼吸恢复率优于纳洛酮。     

An LC-MS Method for Evaluating Photostability of Naloxone Hydrochloride I.V. Infusion

Naloxone is a well-known opioid antagonist indicated for the treatment of CNS （central nervous system） and respiratory depression induced by natural or synthetic opioid in adults and neonates whose mothers have received opioids. While it has been reported that an injection of 0.2 mg/mL of naloxone hydrochloride is physically and chemically stable, data on photostability on continuous i.v. infusion of 0.2 mg/mL of naloxone hydrochloride has not been reported. Therefore, a method was required for assessment of naloxone hydrochloride photostability. A high performance LC-MS （liquid chromatography/mass spectrometry） method was established to evaluate the photostability of naloxone hydrochloride. Injections of naloxone hydrochloride in 0.9% sodium chloride were exposed to artificial light and stored at room temperature （22 ~C） and 37 ~C. Naloxone losses up to 9.79% of its initial concentration when exposed to light at room temperature for 192 h, but the degradation increased up to 14.91% as the storage temperature increase. The disappearance of naloxone hydrochloride was correlated with the appearance of nor-oxymorphonedegradant. Naloxone hydrochloride is photosensitive and degradation increased at highly temperature and light intensity. Therefore, naloxone i.v. infusion solutions should either be protected from light and/or be frequently replaced when being administered to patients.     

Naloxone and baclofen attenuate ethanol's locomotor-activating effects in preweanling Sprague-Dawley rats.

Heterogeneous rat strains appear to be particularly sensitive to the sedative effects of ethanol as adults and insensitive to ethanol's stimulant effects. Recently, the authors found that ethanol induces stimulant effects in preweanling Sprague-Dawley rats. In adult mice, these effects seem to be governed by the mesocorticolimbic dopaminergic pathway, which can be modulated by means of GABA B agonist (baclofen) or opioid antagonist (naloxone) treatments. This study tested whether these pharmacological treatments might reduce the activating effect of ethanol in preweanling Sprague-Dawley rats. Twelve-day-old pups given naloxone (Experiment 1A) or baclofen (Experiment 1B) before ethanol administration were tested in terms of locomotor activity in a novel environment. Naloxone and baclofen significantly reduced the stimulating effect of ethanol but had no effect on locomotor activity patterns in water-treated controls. Blood ethanol levels were not affected by naloxone or baclofen (Experiment 2). During the preweanling period, opioid and GABA B receptors seem to be involved in the stimulating effect of ethanol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blocking, Unblocking, and Overexpectation of Fear: A Role for Opioid Receptors in the Regulation of Pavlovian Association Formation.

Injection of the opioid receptor antagonist naloxone facilitated acquisition of fear to contextual and auditory conditioned stimuli (CSs) in Experiments 1A and 1B. Experiment 2 showed that prior conditioning to a distinctive context blocked conditioning to an auditory CS. Blocking of CS fear was prevented by administrations of naloxone or increases in footshock intensity. Blocking of CS fear was facilitated by decreases in footshock intensity in a naloxone-reversible manner. Experiment 3 showed that compound conditioning of two CSs, each previously and separately paired with shock, produced overexpectation of fear that was reversed by naloxone. These results are consistent with a role for opioid receptors controlling Pavlovian association formation by regulating the discrepancy (A--ΣV) described by R. A. Rescorla and A. R. Wagner (1972). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Histamine H? receptors mediate morphine-induced locomotor hyperactivity of the C57BL/6J mouse": Correction to Mickley.

Reports an error in "Histamine H? receptors mediate morphine-induced locomotor hyperactivity of the C57BL/6J mouse" by G. Andrew Mickley (Behavioral Neuroscience, 1986[Feb], Vol 100[1], 79-84). An incorrect word was inadvertently printed. The last sentence of the introduction (p. 79) should read "This was accomplished by challenging the opiate-stimulated locomotion of the C57BL/6J mouse with injections of antihistamines into the nucleus accumbens/stria terminalis or lateral ventricles." (The following abstract of the original article appeared in record 1986-14026-001.) Locomotor hyperactivity induced in C57BL/6J male mice (N=43) by intraperitoneal morphine sulfate (30 mg/kg) was challenged with intracranial injections of antihistamines or the opiate antagonist naloxone HCl (2 μg). When 75 μg of cimetidine, an H? receptor blocker, was injected into the nucleus accumbens/stria terminalis, it significantly reduced opiate-stimulated locomotion. However, ventricular injections of cimetidine did not significantly alter hyperactivity induced by either morphine or dextroamphetamine sulfate (4 mg/kg), nor did cimetidine depress spontaneous locomotion. Although naloxone eliminated morphine-induced locomotion when injected into either the nucleus accumbens or the ventricles, chlorpheniramine (20 μg), an H? receptor blocker, failed to reduce this behavior. Data suggest that opiate-stimulated locomotion of the C57BL/6J mouse may be partially mediated by histamine H? receptors of the nucleus accumbens or closely adjacent structures. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

纳洛酮对反复脑缺血再灌注小鼠学习记忆的影响及机制

目的: 观察侧脑室注射(intra-cerebroventricular injection,i.c.v)纳洛酮(naloxone hydrochloride,NAL)对反复脑缺血再灌注小鼠学习记忆的影响及机制。方法: 小鼠作侧脑室埋植套管,术后抗感染4 ~ 5 d,然后采用清醒小鼠造成反复脑缺血再灌注模型,电迷宫法观察小鼠学习记忆情况,比色法检测脑内丙二醛含量,放射免疫法测定脑内及血浆内β-内啡呔(β-endorphin,β-Ep)含量。结果: 纳洛酮可以明显改善反复脑缺血再灌注小鼠学习记忆的情况,同时可不同程度地抑制由反复脑缺血再灌注引起的脑内异常升高的丙二醛、β-内啡呔,改善海马CA1 区细胞数目。结论: 纳洛酮对反复脑缺血再灌注损伤有保护作用,其机制可能与抑制脑内升高的丙二醛、β-内啡呔,从而提高海马CA1 区细胞数目有关。     

Naloxone, but not flupenthixol, disrupts the development of conditioned ejaculatory preference in the male rat.

Male rats display a conditioned preference to ejaculate with a female bearing an odor paired previously with copulation to ejaculation. The present study examined the role of endogenous opioid and dopamine systems in this preference. Male rats received saline, the opioid receptor antagonist naloxone, or the dopamine receptor antagonist flupenthixol prior to 10 conditioning trials in a pacing chamber with an almond-scented female. On the final test, all males were injected with saline and given access to 2 females, 1 scented and the other unscented, in an open field. Only males injected with naloxone during training failed to manifest a conditioned ejaculatory preference. These findings suggest that activation of opioid, but not dopamine, systems during sexual interaction are necessary for conditioned ejaculatory preference in male rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociations of the medial and lateral perforant path projections into dorsal DG, CA3, and CA1 for spatial and nonspatial (visual object) information processing.

Medial perforant path plasticity can be attenuated by 2-amino-5-phosphonovaleric acid (APV) infusions, whereas lateral perforant path plasticity can be attenuated by naloxone infusions. The present experiment was designed to evaluate the role of each entorhinal efferent pathway into the dorsal hippocampus for detection of spatial and nonspatial (visual object) changes in the overall configuration of environmental stimuli. Dorsal dentate gyrus infusions of either APV or naloxone attenuated detection of a spatial change, whereas only naloxone infusions disrupted novel object detection. Either APV or naloxone infusions into dorsal CA3 disrupted both spatial and novel object detection. APV infusions into dorsal CA1 attenuated detection of a spatial change, whereas naloxone infusions into dorsal CA1 disrupted novel object detection. These data suggest that each dorsal hippocampal subregion processes spatial and nonspatial (visual object) information from perforant path efferents in a unique manner that is consistent with the intrinsic properties of each subregion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)