神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

钙拮抗剂TMB-8抑制BHQ,NE和KCl引起的培养乳牛基底动脉单个平滑肌细胞内游离钙的升高

用ＡＲＣＭＭＩＣ阳离子测定系统，测量单个细胞内游离钙浓度（［Ｃａ２＋］ｉ），研究８（Ｎ，Ｎ二乙胺）ｎ辛基３，４，５三甲氧基苯甲酸酯（ＴＭＢ８）对培养乳牛基底动脉平滑肌［Ｃａ２＋］ｉ的作用。在细胞外钙浓度为１３ｍｍｏｌ·Ｌ－１时，ＴＭＢ８（３０μｍｏｌ·Ｌ－１）可明显抑制ＢＨＱ，ＮＥ及ＫＣｌ引起［Ｃａ２＋］ｉ的升高。在细胞外钙为零＋ＥＧＴＡ０１ｍｍｏｌ·Ｌ－１时，ＴＭＢ８（１０，３０及１００μｍｏｌ·Ｌ－１）可浓度依赖性地降低静息［Ｃａ２＋］ｉ，ＴＭＢ８（３０μｍｏｌ·Ｌ－１）可几乎完全阻断ＢＨＱ及ＮＥ引起［Ｃａ２＋］ｉ的增加。研究表明ＴＭＢ８降低培养乳牛基底动脉平滑肌［Ｃａ２＋］ｉ的机制，主要是抑制肌浆网Ｃａ２＋的释放，或增加肌浆网对Ｃａ２＋的摄入，并由此间接地抑制细胞外钙的内流。     

氢氯噻嗪对大鼠主动脉收缩及^86Rb外流的影响

氢氯噻嗪（ＨＣＴ）０．１，０．３ｍｍｏｌ·Ｌ＾－１可抑制低浓度ＫＣＬ（〈４０ｍｍｏｌ·Ｌ＾－１），ＮＥ和５－ＨＴ所致大鼠主动脉条收缩，对高Ｋ＾＋（８０ｍｍｏｌ·Ｌ＾－１）去极化时ＣａＣｌ２所致收缩无影响。ＨＣＴ对低浓度ＫＣＬ所致收缩的抑制作用可被ＢａＣｌ２和ＴＥＡ拮抗，不被Ｇｌｉ拮抗。ＨＣＴ３ｍｍｏｌ·Ｌ＾－１可使＾８６Ｒｂ外流增加，此作用可这ＢａＣｌ２拮抗，不被Ｇｌｉ拮抗。ＨＣＴ抑制大鼠主动脉…     

三氟拉嗪对大鼠脑突触体内Ca2＋水平和Ca2＋，Mg2＋─ATP酶活性的作用

用Ｑｕｉｎ２法测得大鼠脑突触体内静息游离Ｃａ２＋浓度（［Ｃａ２＋］ｉ）为８５±１３μｍｏｌ·ｇ－１ｐｒｏｔｅｉｎ．三氟拉嗪（ＴＦＰ）１，５和１０μｍｏｌ·Ｌ－１对静息突触体［Ｃａ２＋］ｉ无明显影响，但能以剂量依赖方式增高６５ｍｍｏｌ·Ｌ－１ＫＣｌ所致突触体［Ｃａ２＋］ｉ升高，从１９２±５８μｍｏｌ·ｇ－１ｐｒｏｔｅｉｎ分别达到２３３±６３，４３１±９９和６６１±１７３μｍｏｌ·ｇ－１ｐｒｏｔｅｉｎ．ＴＦＰ５，１０和５０μｍｏｌ·Ｌ－１分别使突触体Ｃａ２＋，Ｍｇ２＋－ＡＴＰ酶活性降低３１％，４１％和４５％；使Ｍｇ２＋－ＡＴＰ酶活性降低３０％，３６％和３９％，提示ＴＦＰ可能是通过抑制钙调素，进而抑制Ｃａ２＋，Ｍｇ２＋－ＡＴＰ酶活性，使突触体［Ｃａ２＋］ｉ升高，促进神经末梢释放递质     

三七总皂苷对突触体谷氨酸释放及谷氨酸受体特异性结合的影响

目的研究三七皂苷（ＰＮＳ）对突触体谷氨酸（Ｇｌｕ）释放及其与受体特异性结合的影响。方法采用荧光分析法测定突触体谷氨酸释放。结果ｉｐＰＮＳ５０，１００ｍｇｋｇ－１，连续３ｄ明显抑制小鼠自发活动。体外实验发现ＰＮＳ（２００，４００ｍｇＬ－１）抑制Ｃａ２＋依赖性Ｇｌｕ释放，而对Ｃａ２＋非依赖性释放无明显影响；对［３Ｈ］－Ｇｌｕ与谷氨酸受体特异性结合没有作用。结论ＰＮＳ对中枢神经系统的抑制作用至少部分是通过减少突触体谷氨酸释放实现的     

HEK293细胞—— 一种研究受体Ca~(2+)调控功能的理想模型

目的了解ＨＥＫ２９３细胞Ｃａ２＋代谢的生物学特性。方法用Ｆｕｒａ－２荧光探针双波长测定细胞胞浆游离Ｃａ２＋浓度（［Ｃａ２＋］ｉ）方法，观察多种能改变细胞内Ｃａ２＋代谢的药物对天然的和转染了α１Ｂ肾上腺素受体ｃＤＮＡ的ＨＥＫ２９３细胞［Ｃａ２＋］ｉ的影响。结果在含１．５ｍｍｏｌＬ－１ＣａＣｌ２的缓冲液中，ＫＣｌ５０ｍｍｏｌＬ－１和ＢａｙＫ８６４４１０μｍｏｌＬ－１不影响ＨＥＫ２９３细胞的［Ｃａ２＋］ｉ；ｃｙｃｌｏｐｉａｚｏｎｉｃａｃｉｄ（ＣＰＡ０．０１，０．１，１０μｍｏｌＬ－１）能浓度依赖性地引起ＨＥＫ２９３细胞的［Ｃａ２＋］ｉ呈双相升高，其中的Ｃａ２＋内流相不受ｎｉｆｅｄｉｐｉｎｅ（１０μｍｏｌＬ－１）的影响；但可被１ｍｍｏｌＬ－１ＮｉＳＯ４完全抑制。在无Ｃａ２＋的缓冲液中，咖啡因２０ｍｍｏｌＬ－１和ｒｙａｎｏｄｉｎｅ１μｍｏｌＬ－１均不影响ＨＥＫ２９３细胞的［Ｃａ２＋］ｉ。先用ＣＰＡ（３０μｍｏｌＬ－１）耗竭ＨＥＫα１Ｂ细胞内Ｃａ２＋贮存池后，肾上腺素１０μｍｏｌＬ－１能进一步升高［Ｃａ２＋］ｉ。在有Ｃａ２＋或无Ｃａ２＋的缓冲液中，肾上腺素均可引起ＨＥＫα１Ｂ细胞［Ｃａ２＋］ｉ升高。结论ＨＥＫ２９３细胞?     

Effect of taurine on intracellular free calcium concentration in cultured neonatal rat heart cells

在培养的单个ＳＤ乳鼠心肌细胞，观察了牛磺酸对ＫＣｌ，去甲肾上腺素（ＮＥ）和毒毛花苷Ｇ引起的胞浆游离Ｃａ２＋浓度（［Ｃａ２＋］ｉ）变化的影响．当细胞外ＣａＣｌ２浓度为１．３ｍｍｏｌ·Ｌ－１时，牛磺酸１０，２０ｍｍｏｌ·Ｌ－１不影响心肌细胞静息［Ｃａ２＋］ｉ；但能浓度依赖性地抑制３５ｍｍｏｌ·Ｌ－１ＫＣｌ和１μｍｏｌ·Ｌ－１毒毛花苷Ｇ升高［Ｃａ２＋］ｉ的作用．１０μｍｏｌ·Ｌ－１ＮＥ在含Ｃａ２＋的缓冲液中能引起双相的［Ｃａ２＋］ｉ变化，即快速升高相和持续升高相．牛磺酸２０ｍｍｏｌ·Ｌ－１能抑制ＮＥ引起的［Ｃａ２＋］ｉ持续升高，而对快速升高相无显著影响．在无Ｃａ２＋的缓冲液中，牛磺酸不影响ＮＥ升高［Ｃａ２＋］ｉ的作用．结果提示牛磺酸可能通过减少心肌细胞电压依赖性Ｃａ２＋内流和Ｎａ＋／Ｃａ２＋交换而抑制ＫＣｌ，ＮＥ和毒毛花苷Ｇ引起的［Ｃａ２＋］ｉ升高．     

氯化钆对兔项上交感神经节突触传递的影响

用蔗糖间隙法研究氯化钆对离体兔项上交感神经突触传递的影响，低浓度ＧｄＣｌ３（４０－１６０μｍｏｌ．Ｌ＾－＾１）对神经节复合动作电位有易化作用。高Ｃａ＾２＾＋可增强Ｇｄ＾３＾＋的效应；无Ｃ＾２＾＋溶液中Ｇｄ＾３＾＋不显示易化作用。钙通道阻断剂维拉帕米可拮抗Ｇｄ＾３＾＋的易化作用。低浓度ＧｄＣｌ３对复合动作电位后超极化电位和Ｎ波亦有易化作用，但对乙酰胆碱去极化电位则无影响，高浓度ＧｄＣｌ３（０．５－１     

Mobilization of intracellular Ca~(2 ) modulates activation of Na~ /H~ exchange in thrombin-stimulated platelets

目的：研究凝血酶诱导的血小板活化中细胞内钙动员和Ｎａ＋／Ｈ＋交换的关系．方法：Ｆｕｒａ２负载测［Ｃａ２＋］ｉ和ＢＣＥＣＦ负载测ｐＨｉ．结果：凝血酶０１ＩＵ·Ｌ－１引起［Ｃａ２＋］ｉ和ｐＨｉ增加，［Ｃａ２＋］ｉ增加先于ｐＨｉ增加．在无钠溶液中，Ｎａ＋／Ｈ＋交换被抑制而［Ｃａ２＋］ｉ增加不受影响；用尼日利亚菌素（１ｍｇ·Ｌ－１）使胞内酸化可抑制［Ｃａ２＋］ｉ增加．用依他酸（ＥＧＴＡ）阻断外钙内流，胞浆碱化不受影响．伊屋诺霉素加ＥＧＴＡ耗竭胞内钙池时，胞浆硷化效应被取消，且静息ｐＨｉ更低，加入１ｍｍｏｌ·Ｌ－１外钙重新充填钙池，胞浆碱化效应又被恢复．结论：细胞内钙动员调控Ｎａ＋／Ｈ＋交换，后者需［Ｃａ２＋］ｉ增加达一定有效浓度．     

糖基化终产物对培养的大鼠主动脉平滑肌细胞增殖及胞浆游离钙含…

目的：研究糖基化终产物（ＡＧＥＰ）对主动脉平滑肌细胞增殖的影响及其与［Ｃａ＾２＋］ｉ的关系。方法：采用同位素掺入法分别测定ＤＮＡ和蛋白质合成；Ｆｕｒａ２－ＡＭ测定［Ｃａ＾２＋］ｉ。结果：ＡＧＥＰ以浓度、时间相关的方式促进［＾３Ｈ］ＴｄＲ与［＾Ｈ］Ｌｅｕ掺入细胞，随ＡＧＥＰ作用时间、糖化时间延长，掺入率增加明显，ＡＧＥＰ增加［Ｃａ＾２＋］ｉ，与时间、浓度相关，但随ＡＧＥＰ作用时间延长（４０分钟后）而     

神经生长因子改善衰老性记忆障碍及突触机制的探讨

目的　探讨神经生长因子(NGF)改善衰老性记忆障碍的机制。方法　采用开场行为和一次性被动回避反应模型,观察海马内微量注射NGF对衰老小鼠自发活动和记忆巩固过程的影响, 同时用Ca²⁺荧光探针Fura-2/AM和AR-CM-MIC阳离子测定系统测定海马突触体游离钙水平,以³H-Leu为标记物测定海马突触体总蛋白的合成量。结果　NGF使衰老小鼠在新异环境中的自发活动和探究行为明显增多,并显著延长电击后24 h的步入潜伏期(STL); NGF显著降低衰老小鼠海马突触体内的高钙水平,并使海马突触体蛋白质的³H-Leu参入量显著增加。结论　NGF改善衰老性记忆障碍与其降低海马突触体内高钙水平,并由此促进海马突触体蛋白质的合成有关。     

Effects of NMDA receptor antagonists on passive avoidance learning and retrieval in rats and mice

The effects of NMDA antagonists on passive avoidance learning, shock sensitivity and locomotor activity were examined. Pre-training administration of the antagonists 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) in mice and rats resulted in impaired performance in a retention test 24 h later. No such impairment resulted from immediate post-training administration of either compound in either species. In addition neither compound, given only before the retention test, reduced the retention latencies of mice. In rats CPP was similarly ineffective whereas MK-801 reduced retention latencies, but only at a dose which significantly elevated locomotor activity at the time of the retention test. As assessed by vocalization threshold in mice and by the proportion of animals vocalizing in response to the passive avoidance training shock, neither compound produced analgesia. The vocalization threshold was, in fact, slightly reduced by both compounds. MK-801, but not CPP, stimulated locomotor activity in mice. These results indicate that in the passive avoidance task activation of NMDA receptors is involved in memory formation, but is not critical for the maintenance of memory or its retrieval.     

Chronic administration of the Ca(2+) channel blocker amlodipine facilitates learning and memory in mice

Acute administration of the Ca(2+) channel antagonist amlodipine has been shown to facilitate memory for several types of learning in adult animals and to improve retention in aging mice. This study reports three experiments investigating the effect of chronic amlodipine treatment on retention in mice. In the first experiment, groups of mice were treated with either amlodipine or vehicle once a day for 14 days prior to training on a spatial discrimination task. Immediately after training, animals were given a single dose of amlodipine or the vehicle and tested for retention 24 h later. Both groups showed facilitated retention, thereby demonstrating that chronic amlodipine treatment did not produce desensitization to the facilitating effects of a post training treatment. In the second experiment, chronic treatments were administered once daily for 14 days beginning 24 h after training on one-way active avoidance and retention was tested on day 15. Results showed that chronic amlodipine attenuated spontaneous forgetting, but surprisingly, a similar enhancement could be achieved by a single treatment administered 1 day after training. In the third experiment, amlodipine was given either before or immediately after 10 daily training sessions in the one-way active avoidance task. Results showed that chronic treatment accelerated rate of learning. These findings confirm the memory facilitating properties of amlodipine under conditions of chronic drug administration.     

GABAA Receptor Blockade Enhances Memory Consolidation by Increasing Hippocampal BDNF Levels

Memory consolidation is the process by which acquired information is converted to something concrete to be retrieved later. Here we examined a potential role for brain-derived neurotrophic factor (BDNF) in mediating the enhanced memory consolidation induced by the GABA_A receptor antagonist, bicuculline methiodide. With the administration of an acquisition trial in naïve mice using a passive avoidance task, mature BDNF (mBDNF) levels were temporally changed in the hippocampal CA1 region, and the lowest levels were observed 9 h after the acquisition trial. In the passive avoidance task, bicuculline methiodide administration within 1 h of training but not after 3 h significantly increased latency time in the retention trial 24 h after the acquisition trial. Concomitantly, 1 h post-training administration of bicuculline methiodide, which enhanced memory consolidation, significantly increased mBDNF levels 9 h after training compared to those of the vehicle-treated control group. In addition, exogenous human recombinant BDNF (hrBDNF) administration 9 h after training into the hippocampal CA1 region facilitated memory consolidation confirming that the increase in mBDNF at around 9 h after training plays a key role in the enhancement of memory consolidation. Moreover, the increases in latency time and immediate early gene expressions by bicuculline methiodide or hrBDNF were significantly blocked by anisomycin, a protein synthesis inhibitor, K252a, a tyrosine receptor kinase (Trk) inhibitor, or anti-TrkB IgG. These findings suggest that the increase in the level of mBDNF and its function during a restricted time window after training are required for the enhancement of memory consolidation by GABA_A receptor blockade.     

The effects of dexmedetomidine, an alpha 2 agonist, on learning and memory, assessed using passive avoidance and water maze tasks in rats.

The effects of dexmedetomidine, a specific and potent alpha 2 agonist, on the performance of rats in passive avoidance and water maze tasks were studied. Pre-training administration of subanaesthetic dose (9.0 micrograms/kg) of dexmedetomidine impaired the retention of the passive avoidance task (assessed 24 hr after training) but it did not affect the training of this task. Smaller doses (0.3, 0.9 and 3.0 micrograms/kg) did not affect the training or retention of this aversively motivated task. On the other hand, pre-training administration of 0.3 and 0.9 microgram/kg dexmedetomidine impaired the acquisition of the water maze task, whereas larger doses (3.0 and 9.0 micrograms/kg) had no significant effect on spatial learning. Pre-training administration of dexmedetomidine (0.3-9.0 micrograms/kg) increased swimming speed in rats. Only a large dose (300 micrograms/kg) of dexmedetomidine, administered immediately after training, impaired the retention of the passive avoidance task and the acquisition of the water maze task. These data agree with previous findings that pharmacological manipulation of the noradrenergic system affects the retention of aversively-motivated (passive avoidance) tasks. The present results suggest that the dose-response curve of dexmedetomidine for impairment of learning/memory differs between the passive avoidance and water maze tasks.     

Effects of selective inhibition of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) on mice in learning and memory tasks

The purpose of the present study was to examine the effects of 2-(phosphonomethyl)-pentanedioic acid (2-PMPA), a selective inhibitor of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase, glutamate carboxypeptidase II), an enzyme catalyzing the cleavage of glutamate from the neuropeptide N-acetyl-aspartyl-glutamate (NAAG), on memory processes in mice. Long-term memory was evaluated in step-through passive avoidance task while alternation behavior, as a measure involving spatial working memory, was assessed in Y-maze task. Additionally, horizontal activity was evaluated by means of electronically monitored locomotor activity system. The mice were treated with either 2-PMPA (50, 100 and 150 mg/kg i.p.) or N-methyl-d-aspartate (NMDA) receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) at doses of: 0.05, 0.1, 0.15 and 0.2 mg/kg i.p., as a comparator. In the passive avoidance task, the drugs were administered once before or immediately after training, and before retention test. 2-PMPA at the doses used did not affect retention of passive avoidance; however, it increased the latency to enter the dark box during the training day. In the Y-maze task, 2-PMPA (150 mg/kg i.p.) impaired spontaneous alternation and reduced locomotion while the lower dose of 100 mg/kg was ineffective. In the locomotor activity test, 2-PMPA (100 and 150 mg/kg i.p.) did not significantly affect horizontal activity. MK-801 (0.2 mg/kg i.p.) injected before training reduced retention in the passive avoidance task. In the Y-maze task, MK-801 (0.1 mg/kg i.p.) impaired alternation behavior and considerably increased locomotion in the Y-maze and locomotor activity test. These results indicate that NAALADase inhibition may impair alternation behavior.     

Memory and learning impairment induced by dexamethasone in senescent but not young mice

In this study, the memory and learning impairment induced by dexamethasone in young mice and senescent mice were evaluated by step-down inhibitory avoidance task and passive avoidance test. Colorimetric MTT(tetrazole 3-(4,5-dimethylthiazol-2-yl-)-2,5-diphenyltetrazolium bromide) assay and TUNEL staining were used to investigate the influence of dexamethasone on hippocampal neuronal cell death with amyloid beta-protein. It was determined the effect of dexamethasone on intracellular calcium ([Ca(2+)](i)) with amyloid beta-protein 25-35 by fluorescence imaging with a confocal laser microscope using fluo-3 acetoxymethylester (AM) as a fluorescent dye. The effect of dexamethasone on amyloid beta-protein 25-35-induced nuclear factor kappaB (NF-kappaB) was analyzed by western blot. The results showed that twenty one days dexamethasone exposure resulted in an impairment of memory and learning in senescent but not young mice. Pretreatment of isolated hippocampal neurons with dexamethasone increased the vulnerability of the hippocampal neurons to amyloid beta-protein 25-35, enhanced [Ca(2+)](i) and down-regulated the increased level of nuclear NF-kappaB p65 proteins induced by amyloid beta-protein 25-35. These results demonstrated that glucocorticoids could potentiate the neurotoxic action of amyloid beta-protein by further increasing the level of [Ca(2+)](i) and down-regulating the level of nuclear NF-kappaB protein. Since amyloid beta-protein increases in the brain with aging, glucocorticoids potentiation of the neurotoxic action of amyloid beta-protein maybe one of the mechanisms responsible for glucocorticoids-induced memory and learning impairment in senescent but not young mice, which maybe relevance to the etiology of Alzheimer's disease.     

GABAergic modulation of memory with regard to passive avoidance and conditioned suppression tasks in mice

The role of GABAergic neuronal system in learning and memory was investigated using the step-down typed passive avoidance and rapidly learned conditioned suppression tasks in mice. GABA antagonists, picrotoxin and bicuculline, or a GABA synthesis inhibitor, 3-mercaptopropionic acid (3-MP), were administered just after the training test. All of these drugs caused amnesia: they shortened the step-down latency (SDL) and attenuated the conditioned suppression of motility in the retention test conducted 24 h after the administration. Furthermore, we investigated the effect of GABA receptor agonists, muscimol and baclofen, or a GABA transaminase inhibitor, aminooxyacetic acid (AOAA), on these amnesia models. GABA agonists showed an antiamnesic action as follows: in the passive avoidance task, 1) picrotoxin-induced amnesia was antagonized by muscimol, baclofen and AOAA. 2) Bicuculline-induced amnesia was antagonized by muscimol and AOAA but not by baclofen. 3) 3-MP-induced amnesia was antagonized only by muscimol. 4) In the rapidly learned conditioned suppression task, picrotoxin-, bicuculline- and 3-MP-induced amnesia were antagonized by muscimol, baclofen and AOAA. These results suggest that the GABAergic neuronal system plays an important role in the memory retention of passive avoidance and rapidly learned conditioned suppression tasks.     

DDC-Induced amnesia and norepinephrine: A correlated behavioral-biochemical analysis

Diethyldithiocarbamic acid (DDC), a dopamine-B-hydroxylase inhibitor, when injected into rats 30 min to 6 h before training of a passive avoidance task, impaired formation of long-term memory as indicated by performance on a retention test 24 h later. Performance of the task was at its minimum when injection occurred 2 to 4 h prior to training; recovery was evident in animals trained 5 or 6 h after drug treatment. Catecholamine assay of brains of temporally yoked animals showed that norepinephrine depletion followed a time course paralleling that of the amnesia. These findings support the hypothesis that the degree of memory storage, as reflected in performance following training in a passive avoidance task, can be directly correlated with the level of norepinephrine existing at the time of training.     

Substance P enhancement of passive and active avoidance conditioning in mice

In a series of seven experiments we explored the effects of peripherally administered substance P on passive and active avoidance conditioning in mice of two genotypes. The peripheral post-trial administration of substance P significantly enhanced the retention of a single-trial passive avoidance task. This effect was dose dependent; 1 ng/g of substance P enhanced the retention of this habit, whereas higher and lower doses were either less effective or ineffective. In heterogeneous strain (HS) mice, substance P administered before training on an active avoidance task did not alter the rate at which these animals learned this habit. However, animals that had been trained with substance P were significantly more resistant to extinction than were animals that had been injected with vehicle. Similarly, C57Bl/6J mice that had been treated with substance P immediately after active avoidance training were more resistant to extinction than were mice that had been given control injections. The enhancement of retention of the passive avoidance habit with substance P was reversed in animals that had been pretreated with naltrexone. Substance P enhancement of the retention of the passive avoidance habit, and its reversal with naltrexone, was observed in both sham operated and adrenalectomized mice.