共查询到20条相似文献,搜索用时 15 毫秒
1.
Jodi R. SamartgisLeslie Schachte Agnes HaziSimon F. Crowe 《Pharmacology, biochemistry, and behavior》2012,103(2):353-358
Piracetam is an AMPAkine drug that may have a range of different mechanisms at the cellular level, and which has been shown to facilitate memory, amongst its other effects. This series of experiments demonstrated that a 10 mg/kg dose of piracetam facilitated memory consolidation in the day-old chick when injected from immediately until 120 min after weak training (i.e. using a 20% v/v concentration of methyl anthranilate) with the passive avoidance learning task. Administration of piracetam immediately after training led to memory facilitation which lasted for up to 24 h following training. This dose of the AMPAkine was not shown to facilitate memory reconsolidation. These findings support the contention that application of the AMPAkine piracetam facilitates memory using a weak training task, and extend the range of actions previously noted with NMDA-related agents to those which also facilitate the AMPA receptor. 相似文献
2.
Five experiments were conducted to investigated the generality of puromycin's reported effect on disruption on memory of a recently learned task. The first experiment replicated previous work on acquisition to determine the effectiveness of the procedures used. The second investigated the role of puromycin's low pH in memory disruption. The third experiment used short training and extinction sessions to determine if puromycin retarded retention of extinction. The fourth experiment used longer training and extinction sessions and multiple and delayed injections of puromycin, and the fifth experiment attempted to extend puromycin's effect on avoidance extinction to extinction produced in an appetitive operant task. Puromycin disrupted retention of extinction of both shuttle box avoidance in fish and barpressing in rats. The role of puromycin's pH was negligible. 相似文献
3.
L Barbier F Dorandeu C Giroud C Beaup A Foquin R Maury A Alonso A Peinnequin F Canini 《European journal of pharmacology》2012,691(1-3):77-85
Exposure to organophosphorus compounds, either pesticides or chemical warfare agents such as soman or sarin, represents a major health problem. Organophosphorus poisoning may induce seizures, status epilepticus and even brain lesions if untreated. Ketamine, an antagonist of glutamatergic receptors, was recently proved to be effective in combination with atropine sulfate as an anticonvulsant and neuroprotectant in mice and guinea pigs exposed to soman. Organophosphorus exposure may also occur in conditions of contemporary heat exposure. Since both MK-801, a more potent glutamatergic antagonist than ketamine, and atropine sulfate are detrimental for thermoregulation, we evaluated the pathophysiological consequences of ketamine/atropine combinations in a hot environment. Male wistar rats were exposed to 38°C ambient temperature and treated with atropine sulfate and/or ketamine (anesthetic and subanesthetic doses). The abdominal temperature and spontaneous locomotor activity were continuously monitored using telemetry. At the end of heat exposure, blood chemistry and the mRNA expression of some specific genes in the brain were assessed. Unlike MK-801, ketamine did not induce any deleterious effect on thermoregulation in rats. Conversely, atropine sulfate led to heatstroke and depressed the heat-induced blood corticosterone increase. Furthermore, it induced a dramatic increase in Hsp70 and c-Fos mRNA levels and a decrease in IκBα mRNA expression, both suggesting brain aggression. When combined with the anesthetic dose of ketamine, some of the atropine-induced metabolic disturbances were modified. In conclusion, ketamine can be used in hot environment and may even limit some of the biological alterations induced by atropine sulfate in these conditions. 相似文献
4.
Stainless steel cannulae were implanted in the medial hippocampus of 24 rats. The subjects were then trained to press a bar for milk reinforcement. After a fixed amount of training the animals were divided into four groups. A control group received injections of Holman's ringer (via the cannulae) while each of three experimental groups received a different dose of magnesium pemoline. The animals then performed an additional number of bar presses. Twenty-four hours later the time and number of bar presses to an extinction criterion were measured. The low and medium drug-dose group exhibited increased resistance to extinction. The results were discussed with regard to the effect magnesium pemoline has on performance variables and RNA synthesis.This work was supported by Australian Research Grants Committee and Sigma Xi funds to Dr. J. C. Saunders. The authors gratefully acknowledge the assistance of Mr. G. R. Bock and Mrs. J. Sack and thank Abbott Laboratories for supplying the drug. 相似文献
5.
Chronic treatment (2 weeks) with piracetam (500 mg/kg, once daily PO) elevatedm-cholinoceptor density in the frontal cortex of aged (18 months) female mice by about 30–40%, but had no effect onm-cholinoceptor density in the frontal cortex of young (4 weeks) mice. The effect of piracetam onm-cholinoceptor density as determined by the specific binding of tritiated QNB was not affected by concomitant daily treatment with either choline (200 mg/kg) or scopolamine (4 mg/kg). It is concluded that the effect of piracetam onm-cholinoceptor density could explain the positive effects which have been reported for combinations of cholinergic precursor treatment with piracetam on memory and other cognitive functions in aged experimental animals and patients and could also represent part of the possible mechanism of action of piracetam alone. 相似文献
6.
Abstract
Rationale. Previous results demonstrated that pretreatment with lobeline attenuates d-methamphetamine self-administration in rats.
Objective. The present experiments determined if lobeline serves as a reinforcer, if it decreases d-methamphetamine-induced reinstatement of d-methamphetamine self-administration, and if it activates the mesolimbic and nigrostriatal dopamine (DA) pathways in Sprague-Dawley
male rats.
Methods. The ability of intravenous (IV) lobeline (0.015–0.15 mg/kg per infusion) to engender responding and the ability of lobeline
(0.015 and 0.05 mg/kg per infusion) to substitute for d-methamphetamine was determined using the self-administration paradigm. Experiments were also performed to determine if lobeline
(1.0 and 3.0 mg/kg) reinstates responding for d-methamphetamine or alters the ability of d-methamphetamine (1.0 mg/kg per infusion) to reinstate responding following extinction. The effect of lobeline (3.0 mg/kg)
or d-methamphetamine (1.0 and 3.0 mg/kg) on DA and dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens and striatum
were also determined.
Results. Lobeline was not self-administered and did not substitute for d-methamphetamine. Also, lobeline did not reinstate responding for d-methamphetamine following extinction nor did it alter d-methamphetamine-induced reinstatement. Furthermore, lobeline did not alter DA or DOPAC levels in the either the nucleus accumbens
or striatum.
Conclusions. Taken together, the present results indicate that lobeline decreases d-methamphetamine self-administration by decreasing reward, not by acting as a substitute reinforcer.
Electronic Publication 相似文献
7.
Shi HS Luo YX Xue YX Wu P Zhu WL Ding ZB Lu L 《Pharmacology, biochemistry, and behavior》2011,98(2):299-303
Relapse induced by exposure to cues associated with drugs of abuse is a major challenge to the treatment of drug addiction. Drug seeking can be inhibited by manipulation of the reconsolidation of drug-related memory. Sleep has been proposed to be involved in various memory processes. However, the role of sleep in drug reward memory is not clear. The present study used conditioned place preference to examine the effects of total sleep deprivation on retrieval and reconsolidation of morphine reward memory in rats. Six-hour total sleep deprivation had no effect on the retrieval of morphine reward memory. However, sleep deprivation from 0-6 h, but not 6-12 h, after re-exposure disrupted the reconsolidation of morphine reward memory. This impairment was not attributable to the formation of an aversive associative memory between the drug-paired context and sleep deprivation. Our findings suggest that sleep plays a critical role in morphine reward memory reconsolidation, and sleep deprivation may be a potential non-pharmacotherapy for the management of relapse associated with drug-related memory. 相似文献
8.
Mierzejewski P Siemiatkowski M Radwanska K Szyndler J Bienkowski P Stefanski R Kaczmarek L Kostowski W 《Neuropharmacology》2006,51(2):367-373
The aim of the present study was to assess the role of de novo protein synthesis in the acquisition and extinction of cocaine self-administration. In a first experiment, rats were trained to respond for intravenous cocaine infusions (0.3 mg/kg) and a protein synthesis inhibitor, cycloheximide (CHX; 3 mg/kg, s.c.) was injected immediately after each self-administration session. In a second experiment, rats were allowed to acquire cocaine self-administration and CHX was injected immediately after subsequent extinction sessions. CHX impaired the acquisition, but not extinction, of cocaine self-administration. In control experiments, CHX (3 mg/kg) blocked c-Fos protein expression after foot-shock stress and impaired the acquisition of conditioned freezing but did not inhibit spontaneous locomotor activity and sucrose drinking. Our results suggest that: i) the acquisition and extinction of cocaine-reinforced behaviour have a different molecular basis; and ii) only the former process requires de novo protein synthesis. 相似文献
9.
Ward A. Rodriguez Marici Y. Phillips Susan B. Rodriguez Joe L. Martinez Jr 《Psychopharmacology》1993,112(2-3):366-370
The effect of cocaine administered prior to memory reactivation on the subsequent acquisition of an avoidance response was investigated. Two noncontingent footshocks were administered to rats in the black compartment of a one-way avoidance chamber. Twenty-four hours later, cocaine or saline was administered 5 min prior to a 30-s reactivation treatment consisting of re-exposure to selected stimuli present during the initial conditioning. Subjects were trained 24 h later to move from the chamber's black compartment to its white compartment in order to avoid a footshock. Intermediate (5.0 or 7.5 mg/kg IP), but not low (3.3 mg/kg IP) or high (11.25 or 16.88 mg/kg IP), doses of cocaine given prior to the reactivation treatment enhanced later acquisition of the one-way administered prior to the reintroduction of cues associated with a conditioning episode can modulate memory processes, and that the dose-response function for this effect is U-shaped. The avoidance performance of rats that received cocaine (5.0 mg/kg IP) 3 h after the reactivation treatment did not differ from that of saline-treated control subjects, suggesting that the conjoint neural activity elicited by cocaine and exogenous retrieval cues is necessary for potentiation of memory retrieval or reconstruction processes.Some of these data are reported in abstract form in Rodriguez et al. (1992). Injections of cocaine prior to memory reactivation facilitate later learning of an avoidance response in rats. Soc Neurosci Abstr 18:1573 相似文献
10.
Rationale. AIT-082 (Neotrofin), a hypoxanthine derivative, has been shown to improve memory in both animals and humans. In animals,
adrenal hormones modulate the efficacy of many memory-enhancing compounds, including piracetam and tacrine (Cognex).
Objective. To investigate the role of adrenal hormones in the memory-enhancing action of AIT-082.
Methods. Plasma levels of adrenal hormones (corticosterone and aldosterone) in mice were significantly reduced by surgical or chemical
(aminoglutethimide) adrenalectomy or significantly elevated by oral administration of corticosterone. The effects of these
hormone level manipulations on the memory-enhancing activity of AIT-082 and piracetam were evaluated using a cycloheximide-induced
amnesia/passive avoidance model.
Results. As previously reported by others, the memory enhancing action of piracetam was abolished by adrenalectomy. In contrast, the
memory enhancement by 60 mg/kg AIT-082 (IP) was unaffected. However, a sub-threshold dose of AIT-082 (0.1 mg/kg, IP) that
did not improve memory in control animals did improve memory in adrenalectomized animals. These data suggested that, similar
to piracetam and tacrine, the memory enhancing action of AIT-082 might be inhibited by high levels of adrenal hormones. As
expected, corticosterone (30 and 100 mg/kg) inhibited the action of piracetam, however no dose up to 100 mg/kg corticosterone
inhibited the activity of AIT-082.
Conclusions. These data suggest that while AIT-082 function is not dependent on adrenal hormones, it is modulated by them. That memory
enhancement by AIT-082 was not inhibited by high plasma corticosterone levels may have positive implications for its clinical
utility, given that many Alzheimer's disease patients have elevated plasma cortisol levels.
Electronic Publication 相似文献
11.
Otto L. Wolthuis 《Pharmacology, biochemistry, and behavior》1981,15(2):247-255
The effects of etiracetam, a structural analogue of piracetam, were investigated in rats on Y-maze discrimination acquisition, on open field behaviour, on one-trial passive avoidance learning and on shuttlebox acquisition and extinction. The results indicate that this drug significantly enhances acquisition and may improve retention without having any detectable effects on spontaneous behaviour, not even in very high doses (500 mg/kg IP). Sensitivity to footshock, measured as “flinch” thresholds, was not altered by etiracetam in doses of 25 or 100 mg/kg IP. For a shuttlebox task the effective dose-range lies between 20–30 mg/kg IP, provided pretreatment during 4 days is given. Without pretreatment, i.e. when the drug is only administered during the relatively fast acquisition in the shuttlebox, it was found that acquisition was not enhanced, but extinction of the acquired behaviour was significantly inhibited. The effects of etiracetam can be found at lower dose-levels than with piracetam and also in tests (passive avoidance, shuttlebox) in which piracetam has no or only marginal effects. 相似文献
12.
Susan J. Sara 《Psychopharmacology》1986,89(3):307-310
Rats were trained in a complex maze task for food reward. After a 25-day retention interval, they made more errors than at the last training trials. This forgetting was alleviated by pretest treatment with haloperidol. The same dose of haloperidol had no effect on acquisition or performance when injected during training. The results were replicated, but smaller doses were found to be inactive. The possibility that the effect might be mediated through the noradrenergic system is considered. 相似文献
13.
Maria G. Genkova-Papazova Maria B. Lazarova-Bakarova 《European neuropsychopharmacology》1996,6(4):285-290
Deficit in active and inhibitory avoidance behaviour has been found in pentylenetetrazole (PTZ)-kindled rats. This supports the view that memory deficit is an integral part of epilepsy. In the present study we examined the effect of the nootropic drugs piracetam and fipexide on memory deficit induced by PTZ-kindling in shuttle-box- and step-down-trained rats. The retention in piracetam- and fipexide-treated animals was significantly improved compared to the kindled controls. The mechanisms of action of the two drugs are considered. The favourable effects of nootropic drugs in cases of amnesia provoked by PTZ-kindling might be of interest in clinical practice. 相似文献
14.
The interaction between cholecystokinin and endogenous opioid systems on rewarding responses was examined. Motivational effects induced by peripheral administration of a complete inhibitor of enkephalin catabolism, RB 101 or the CCKB antagonist PD-134,308, and by both compounds in combination were evaluated in the conditioned place preference test in rats. RB 101 (5, 10, 20, 40 and 80 mg/kg, IP, and 20 mg/kg, IV) given alone produced a bell-shaped dose-effect function. A significant increase of the preference for the drug-associated compartment was only observed at doses of 10 and 20 mg/kg (IP). The effect observed with morphine was stronger, and all the doses used of this compound (1.25, 2.5 and 5 mg/kg, SC) were found to be active. These results suggest that the inhibitor of enkephalin catabolism has weak rewarding properties. Pretreatment with the CCKB antagonist PD-134,308 (0.1, 0.3, 1 and 3 mg/kg, IP) alone failed to produce a reliable aversion or preference on the paradigm studied. When PD-134,308 (0.3 mg/kg, IP) was coadministered with a subthreshold dose of morphine (0.6 mg/kg, SC) or RB 101 (5 mg/kg, IP), a conditioned place preference was observed, indicating that the CCKB antagonist facilitated the motivational responses induced by endogenous enkephalins as compared to morphine. This suggests that endogenous cholecystokinin, acting through CCKB receptors, modulates the rewarding effects of endogenous enkephalins. 相似文献
15.
Tamoxifen and toremifene impair retrieval, but not acquisition, of spatial information processing in mice 总被引:3,自引:0,他引:3
The present study examines the effects of tamoxifen (TAM) or toremifene (TOR), two triphenylethylene antiestrogen agents, on spatial information in mice by using Morris water maze. In a 30-s free swim trial, the TAM- or TOR-treated mice (intraperitoneally, 30 min before test) spent shorter time than the blank control mice in target quadrant. Compared to saline control group, animals exposed to TAM (1-10 mg/kg i.p., once a day for 5 days) or TOR (3-30 mg/kg i.p., once a day for 5 days) did not show significant difference on the acquisition of place task in Morris water maze. These results suggest that TAM, at the doses of 1-10 mg/kg, and TOR, at the doses of 3-30 mg/kg, impair the retrieval, but not the acquisition, of spatial information task in Morris water maze. It seems, however, that TOR is more potent than TAM on impairing memory retrieval. 相似文献
16.
Rationale and objectives Ethanol ataxia experiments with rats investigated cue effects on conditioned tolerance. Spontaneous recovery (SR) was assessed 1 day and 18 days after extinction with conditioned stimuli (CSs) paired or unpaired with an ethanol unconditioned stimulus (US). Behavioral tolerance was assessed by not tilting the apparatus during conditioning. Non-associative processes were assessed post-conditioning with or without a buzzer cue. Boutons (1993, Psychol Bull 114:80–99) memory theory was tested using an extinction cue and an associatively neutral cue presented during SR testing.Methods Tolerance was conditioned to a room + strobelight CS by ethanol injections experienced on a tilting floor (standard conditioning). Controls received no ethanol or ethanol, either during the CS without the floor tilting or 11 h post-CS. SR testing occurred 1 day or 18 days after extinction (experiment 1). Conditioning was followed by tolerance and CR tests either with or without a 15-s buzzer cue (experiment 2). In extinction, the CS and cue occurred without ethanol; the cue occurred before 7% or none of the extinction trials. Testing occurred 18 days after extinction with or without that cue (experiment 3), or with an equally familiar (neutral) cue presented before conditioning (experiment 4). Results Tolerance developed without floor tilting. CS–US unpairings prevented tolerance. Tolerance SR occurred 18 days but not 1 day after extinction only after CS–US pairings (experiment 1). Post-conditioning tests showed no unconditioned effects of the cue (experiment 2). Testing with no cue 1 day after extinction with the cue resulted in no tolerance increase. The extinction cue reduced SR (experiments 3 and 4); the neutral cue did not (experiment 4).Conclusions Cues correlated with extinction reduce SR. Non-associative and practice processes, Boutons (1993, Psychol Bull 114:80–99) memory theory, alternative interpretations, and clinical implications are discussed.This research was supported by funding from Denison University. 相似文献
17.
The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of contextual fear memory and spatial memory in rats 总被引:2,自引:2,他引:0
Rationale Previous studies demonstrated that pharmacological blockade of CB1 cannabinoid receptors decreases the extinction of conditioned fear and spatial memory in rodents. However, the effects of CB1 cannabinoid receptor activation in this response remain unclear.Objectives To evaluate the effects of the cannabinoid agonist WIN 55,212-2 (WIN) and the cannabinoid antagonist SR 147778 (SR) on the extinction of contextual fear memory in rats 24 h or 30 days after fear conditioning.Methods For fear conditioning, rats were placed in the conditioning chamber for 3 min and received a 1-s electric foot shock (1.5 mA). Retrieval testing consisted of a 3-min exposure to the conditioning chamber and extinction training consisted of successive 9-min exposures at 24-h intervals. Rats were also evaluated in the open field and water maze reversal task.Results The administration of SR (1.0 mg/kg, i.p.) and WIN (0.25 mg/kg, i.p.) before extinction training disrupted and facilitated, respectively, the extinction of 24 h contextual fear memory. These effects were not related to any disturbance in memory retrieval, unconditioned freezing expression, or locomotor activity. WIN (0.25 mg/kg, i.p.) also facilitated the extinction of 30-day-old contextual fear memory, while the prior administration of SR (0.2 mg/kg, i.p.) antagonized this response. The facilitative effect of WIN on memory extinction does not seem to be specific for contextual fear memory because it was also observed in the water maze reversal task.Conclusions These results suggest cannabinoid receptor agonists as potential drugs to treat anxiety disorders related to the retrieval of aversive memories.Part of this study was presented at the 18th European College of Neuropsychopharmacology Congress, Amsterdam, The Netherlands, 22–26 October 2005. 相似文献
18.
苯磺酸左旋氨氯地平联用脑复康治疗血管性痴呆的临床研究 总被引:3,自引:0,他引:3
目的:观察苯磺酸左旋氨氯地平联用脑复康治疗血管性痴呆(VD)的疗效。方法:将66例VD患者随机分为治疗组、对照组各33例。治疗组用苯磺酸左旋氨氯地平2·5~5mg,每日1次,脑复康0·8g,每日3次,共服3个月;对照组用脑复康0·8g,每日3次,共服3个月。其他根据血糖、血压、血脂相应基础治疗,观察3个月。治疗前、后用简易精神状态评估量表(MMSE)、日常生活功能量表(ADL)、长谷川痴呆量表(HDS)、痴呆严重程度临床评定量表(WMS),评价2组患者认知功能、智能状态。结果:治疗组用药后MMSE(22·48±3·25)分,ADL(25·16±8·96)分,HDS(23·14±2·91)分,WMS(71·14±19·01)分;对照组用药后MMSE(20·56±3·18)分,ADL(29·74±13·01)分,HDS(20·41±6·25)分,WMS(60·35±20·60)分。治疗组较对照组症状明显改善,差异有统计学意义(P<0·05或P<0·01)。结论:苯磺酸左旋氨氯地平联用脑复康,可明显改善患者的认知功能和智能状态,提高生活质量,治疗VD有效。 相似文献
19.
高效液相色谱法测定吡拉西坦片的含量 总被引:2,自引:0,他引:2
目的:探讨灵敏、准确测定吡拉西坦片含量的方法.方法:采用Alltima C8柱(250.0 mm×4.6 mm,5 μm),以甲醇 水(50∶50)为流动相,流速1.0 mL8226;min 1,检测波长210 nm.结果:吡拉西坦的线性范围为25~150 mg8226;L 1,r=1.000,平均回收率99.7%,RSD=0.37%(n=9).结论:该方法灵敏、准确,可作为吡拉西坦片含量测定的方法. 相似文献
20.
吡拉西坦注射液治疗高颅内压66例 总被引:1,自引:0,他引:1
目的探讨吡拉西坦注射液降低颅内压的临床疗效。方法将黔江中心医院2010年5月至2011年5月收治的颅脑损伤、脑出血非手术治疗患者132例,随机分为研究组和对照组,每组66例。研究组静脉快速滴注20%吡拉西坦注射液,对照组静脉快速滴注20%甘露醇注射液。所有患者均采用持续颅内压监护或定时腰椎穿刺测颅内压。结果研究组显效8例,有效28例,进步28例,无效2例;对照组显效6例,有效26例,进步32例,无效2例。两组总有效率均为96.97%,无显著性差异(P>0.05)。用药期间研究组未观察到与所用药品有关的不良反应。结论吡拉西坦注射液脱水、降颅内压效果明显,安全可靠,无明显不良反应。 相似文献