发育期铅染毒对大鼠学习和记忆的持续性效应

目的研究不同发育期铅染毒对大鼠学习和记忆的持续性效应。方法大鼠分别在断乳前和断乳后进行铅染毒，分别测试20、40和60天龄大鼠Y迷宫学习、短时记忆和长时记忆能力。结果(1)断乳前铅染毒组大鼠20天龄时，0、10min和24h逃避达标率显著低于对照组；停止染毒40d后，10min逃避达标率与对照组相比，差异无显著性；但0min和24h逃避达标率显著低于对照组。(2)断乳后，铅染毒组大鼠0min和24h逃避达标率显著低于对照组，24h逃避达标率显著高于断乳前铅染毒组。结论(1)断乳前铅染毒可损伤大鼠的空间学习、短时和长时记忆能力；停止染毒后短时记忆可得到恢复，而学习和长时记忆的损伤仍持续存在。(2)断乳后铅染毒可损伤大鼠的空间学习和长时记忆能力，但损伤较断乳前铅染毒轻。     

Comparison between the effects of ethanol and diazepam on spatial working memory in the rat

 The present study compared the effects of ethanol and diazepam on a task that allows for the assessment of both spatial working memory and the acquisition of spatial information within each day. During the first trial of each day, subjects were shown the spatial location of a food reward on a six-arm radial-arm maze. During nine subsequent free-choice trials, subjects were reinforced for returning to that same spatial location. The location of the food reward varied across days. Thus, choosing correctly on any given trial required subjects to remember where food had been received during the previous trials of that day. The effects of ethanol and diazepam on working memory were assessed by analyzing the overall number of errors committed during the nine free-choice trials of each day. The effects of ethanol and diazepam on within-day acquisition were assessed by comparing the number of errors committed during the first three trials of each day to the number of errors committed during the last three trials of each day. Ethanol and diazepam both produced dose-dependent increases in working memory errors, and both did so without impairing within-day acquisition. The results of the present study provide further evidence of the similarities between the effects of ethanol and benzodiazepine receptor agonists on learning and memory, and are consistent with the hypothesis that ethanol’s potentiation of GABA at GABA_A receptors contributes to the learning and memory impairments produced by ethanol. Received: 7 January 1997 / Final version: 17 April 1997     

High ethanol and acetaldehyde impair spatial memory in mouse models: opposite effects of aldehyde dehydrogenase 2 and apolipoprotein E on memory

Aldehyde dehydrogenase 2 deficiency may directly contribute to excess acetaldehyde (AcH) accumulation after ethanol (EtOH) drinking and AcH mediates some of the behavioral effects of EtOH. Apolipoprotein E has been suggested to be involved in the alteration of attention and memory. We have chosen Aldh2-knockout (Aldh2-KO), ApoE-KO, and their wild-type (WT) control mice to examine the effects of EtOH and AcH on spatial memory and to compare the possible relationship between genetic deficiency and memory using two behavioral assessments. Mice were trained for 4 days, with EtOH (0.5, 1.0, 2.0 g/kg) being given intraperitoneally on day 4. A probe trial was given on day 5 in the non-EtOH state in the Morris water maze (MWM). The results showed that 2.0 g/kg EtOH increased errors, indicating memory impairment on the eight-arm radial maze (RAM) for all the mice studied. One gram per kilogram EtOH impaired the performance of Aldh2-KO and ApoE-KO mice, but not WT mice. We found similar effects of EtOH on the MWM performance, with 2.0 g/kg EtOH increasing the latencies. One gram per kilogram EtOH increased the latencies of Aldh2-KO and WT mice, but not ApoE-KO mice. The 2.0 g/kg EtOH-induced memory impairment in Aldh2-KO mice was greater, suggesting an AcH effect. Furthermore, time spent on the probe trial was shorter in mice that had previously received 2.0 g/kg EtOH. ApoE-KO mice learned more slowly, while Aldh2-KO mice learned more quickly. Both the RAM and MWM results suggest that high EtOH and AcH impair spatial memory in mice, while lower doses do not have consistent memory effects. In addition, we conclude that genetic differences might underlie some of EtOH's effects on memory.     

The effects of ethanol and lead,alone and in combination,on the severity of arrhythmias induced by coronary artery occlusion,and by noradrenaline,in anaesthetised rats

The aim of this study was to investigate whether chronic (3 or 10 months) administration, via the dinking water, of lead (25 ppm) and/or ethanol (25% v/v) altered the susceptibility of the heart to arrhythmias induced either by coronary artery occlusion or noradrenaline infusion in pentobarbitone-anaesthetised male Sprague-Dawley rats. The cardiac effects of acute intravenous infusions of ethanol (17, 33 and 66 mg kg^–1 min^–1) were also measured. Chronic exposure to ethanol and/or lead in the drinking water had no marked effect on the severity of arrhythmias occurring within the initial 30 min of coronary artery occlusion. In control rats and in those administered ethanol and/or lead for 10 months, noradrenaline (16 g kg^–1 min^–1 given IV 1 h post-occlusion for a 15-min period) induced a similar number of ectopic beats during the infusion period, although these arrhythmias persisted beyond the infusion period in treated animals only. There was a significant accummulation of lead in the bone but not in the blood of lead-treated rats. Blood ethanol concentrations varied considerably between animals, ranging from 0 to 319 mg%. Ethanol (66 mg kg^–1 min^–1) given acutely and yielding a blood concentration of 174 mg % had a slight antiarrhythmic effect in this model.     

Differential effects of chronic haloperidol and olanzapine exposure on brain cholinergic markers and spatial learning in rats

Abstract Rationale. In psychiatric patients, haloperidol (HAL) induces a number of adverse extrapyramidal and cognitive symptoms, which appear to be less problematic with olanzapine (OLZ). In animals, HAL may initiate a number of harmful effects on central nervous system neurons, including damage to cholinergic pathways – an effect that could be especially deleterious to those experiencing memory dysfunction. The identification of the neurobiological substrates of such effects in animal models may help to improve the algorithms used for proper drug selection especially for long-term neuroleptic use. Objectives. The aim of this study was to compare the effects of chronic (45-day and 90-day), continuous oral exposure to HAL with OLZ for effects on cognitive performance and cholinergic markers in rats. Methods. After chronic neuroleptic exposure (and a 4-day washout) spatial memory performance was measured in a water maze task, and choline acetyltransferase (ChAT) immunoreactivity was assessed with immunofluorescence staining. Results. In water maze experiments, HAL and OLZ (relative to vehicle) administered for 90 days (but not 45 days) significantly impaired learning performance (i.e., higher mean latencies across several trials to reach a hidden platform). HAL administered for 90 days was associated with impairment across a greater number of trials than OLZ and it also impaired probe trial performance, as indicated by a reduced number of crossings over the previous platform area (when compared with OLZ or vehicle). Both 45 days and 90 days of HAL treatment reduced ChAT staining in the cortex and hippocampus when compared with OLZ or vehicle. Conclusions. The results in the rat suggest that OLZ (relative to HAL) may be more desirable as an antipsychotic for patients suffering from memory dysfunction especially for those in which cholinergic deficits may already be present. Electronic Publication     

天麻素对癫疒间大鼠海马氧化应激水平的影响

目的研究天麻素对戊四氮(PTZ)致疒间大鼠海马氧化应激水平的影响。方法将30只成年Wistar大鼠随机分为正常对照(NC)组、癫疒间模型(PTZ)组、天麻素(GS)组,观察三组大鼠的行为学和脑电图的变化,采用比色法检测大鼠海马超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力和丙二醛(MDA)含量的变化。结果与PTZ组比较,GS组大鼠癫疒间发作程度减轻,脑电图明显改变,海马组织中SOD和GSHPx活力增加,M DA含量明显减少(P<0.01)。结论天麻素可通过增加癫疒间大鼠海马SOD、GSH-Px活力、抑制M DA的产生,从而影响氧化应激水平,达到对抗癫疒间的效果。     

Role of Nrf2 in preventing ethanol-induced oxidative stress and lipid accumulation

Oxidative stress and lipid accumulation play important roles in alcohol-induced liver injury. Previous reports showed that, in livers of nuclear factor erythroid 2-related factor 2 (Nrf2)-activated mice, genes involved in antioxidant defense are induced, whereas genes involved in lipid biosynthesis are suppressed. To investigate the role of Nrf2 in ethanol-induced hepatic alterations, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation, were treated with ethanol (5 g/kg, po). Blood and liver samples were collected 6 h thereafter. Ethanol increased alanine aminotransferase and lactate dehydrogenase activities as well as thiobarbituric acid reactive substances in serum of Nrf2-null and wild-type mice, but not in Nrf2-enhanced mice. After ethanol administration, mitochondrial glutathione concentrations decreased markedly in Nrf2-null mice but not in Nrf2-enhanced mice. H₂DCFDA staining of primary hepatocytes isolated from the four genotypes of mice indicates that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. Ethanol increased serum triglycerides and hepatic free fatty acids in Nrf2-null mice, and these increases were blunted in Nrf2-enhanced mice. In addition, the basal mRNA and nuclear protein levels of sterol regulatory element-binding protein 1(Srebp-1) were decreased with graded Nrf2 activation. Ethanol further induced Srebp-1 mRNA in Nrf2-null mice but not in Nrf2-enhanced mice. In conclusion, Nrf2 activation prevented alcohol-induced oxidative stress and accumulation of free fatty acids in liver by increasing genes involved in antioxidant defense and decreasing genes involved in lipogenesis.     

Effects of developmental lead exposure on inhibitory avoidance learning and glutamate receptors in rats

Chronic lead (Pb) exposure during development is known to produce learning deficits. AMPA and NMDA receptors have been shown to participate in the synaptic mechanisms involved in certain forms of learning and memory. We investigated whether the effects of Pb on AMPA and NMDA receptors are associated with Pb-induced impairment in learning and memory. Rats were exposed to 0.2% lead acetate at different developmental stages including a maternally exposed group (including gestation and lactation period), a postweaning exposed group, and a continuously exposed group. Lead treatment impaired learning acquisition, but not memory retention in step-down avoidance learning task in all treatment groups. In parallel with the behavioral data, autoradiographic analyses of brain sections indicated that the [³H]AMPA binding was decreased in the CA1 and dentate gyrus of the hippocampus and entorhinal cortex in all three Pb-exposed groups. However, an increase in [³H]MK801 binding was only observed in CA1 of the hippocampus in the continuously Pb-exposed rats. The findings suggest that alterations in AMPA receptor may contribute to the Pb-induced deficits in learning acquisition of inhibitory avoidance.     

Protective effect of Aquilegia vulgaris (L.) against lead acetate-induced oxidative stress in rats

Oxidative stress has been proposed as a possible mechanism involved in lead toxicity. The current study was carried out to evaluate the antioxidant activity of the ethanol extract of Aquilegia vulgaris (L.) against lead acetate (LA)-induced oxidative stress in male rats. Tested animals were treated orally with A. vulgaris extract (100 ppm) in combination with, before, or after LA treatment (20 ppm). The results indicated that the extract alone did not induce any significant changes in body weight gain, food intake, serum biochemical chemistry or the histological picture of the liver and kidney. However, it increased significantly the level of Glutathione (GSH). On the other hand, LA decreased food intake, body weight gain and induced oxidative stress as indicated by the significant changes in serum biochemical parameters and histological picture of liver and kidney and increased lipid peroxide and reduces GSH levels in liver tissues. The extract succeeded to improve the histological pictures of liver and kidney and the biochemical parameters towards the normal values of the control. Moreover, this improvement was pronounced in the animals treated with the extract after LA intoxication.     

Subacute effects of low dose lead nitrate and mercury chloride exposure on kidney of rats

Lead nitrate and mercury chloride are the most common heavy metal pollutants. In the present study, the effects of lead and mercury induced nephrotoxicity were studied in Wistar rats. Lead nitrate (LN, 45 mg/kg b.w/day) and mercury chloride (MC, 0.02 mg/kg b.w/day) and their combination were administered orally for 28 days. Four groups of rats were used in the study: control, LN, MC and LN plus MC groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in kidney tissues were investigated in all treatment groups. LN and MC caused severe histopathological changes. It was shown that LN, MC and also co-treatment with LN and MC exposure induced significant increase in serum urea, uric acid and creatinine levels. There were also statistically significant changes in antioxidant enzyme activities (SOD, CAT, GPx and GST) and lipid peroxidation (MDA) in all groups except control group. In this study, we showed that MC caused more harmful effects than LN in rats.     

Differential experience following developmental lead exposure: effects on brain and behavior

Long Evans hooded rat pups were exposed to lead (Pb) via the maternal milk supply from Postnatal Day 1 (PN 1) to PN 25. Mothers were fed diets containing either 4% Pb CO3 (High Pb), 0.4% Pb CO3 (Low Pb) or 2.2% Na2 CO3 (Controls) throughout this period. Pups were weaned at PN 30 and littermates randomly assigned to either an Enriched or Isolated environment for a period of 30 days. Increases in activity levels and decreases in passive avoidance latencies were observed in Pb exposed animals. However, there were minimal effects due to Pb on symmetrical maze performance. Experience in the enriched environment had no effect on open field activity levels but resulted in a marked reduction in symmetrical maze errors. While enrichment had no effect on passive avoidance performance in High Pb animals, it was capable of raising latencies in Low Pb animals to Control values. Thus, the therapeutic value of environmental enrichment in Pb exposed animals depends on both the task employed and the severity of the pre-enrichment brain damage. From both brain regional analysis and behavioral testing results, it appeared that the hippocampus was a major site of Pb action. From comparison of blood Pb levels of our animals and those reported in children, it became apparent that the rat may have a greater tolerance for Pb, and as such, caution must be used in making direct comparisons between the two species in terms of blood Pb levels.     

Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats

Learning/memory deficits in senescent animals are widely used as a tool to evaluate the therapeutic potential of agents for treatment of age-associated cognitive dysfunction. As assessed in the Morris water maze test, aged (21–24 months) rats showed a variable loss of spatial memory. Aged non-impaired rats performed as well as young subjects, while aged impaired rats exhibited a severe and persistent place-navigation, deficit. Passive avoidance retention was similarly affected in the two aged subpopulations. Chronic oral administration of phosphatidylserine (50 mg/kg/day for up to 12 weeks), a pharmacologically active phospholipid, was found to improve both the spatial memory and the passive avoidance retention of aged impaired rats. Results are discussed with reference to the phosphatidylserine-induced improvement of age-associated deterioration of brain functions in rats.We are grieved to record the unexpected, death of Professor L. Valzelli. He was a scientist of merit and a great humanitarian     

纳洛酮对慢性酒精中毒学习记忆障碍大鼠脑内阿片肽含量的影响

目的：研究慢性酒精中毒对大鼠空间学习记忆的影响、脑区内阿片肽含量的变化，及其阿片受体拮抗剂纳洛酮的治疗作用。方法：3周龄雄性SD大鼠分为4组：给A、B组大鼠自由饮用由含6％逐渐递增至15％（v／v）的乙醇水溶液8周，建立慢性酒精中毒模型，而C、D组自由饮水；8周后B、D大鼠连续10天腹腔注射纳洛酮，A、C组腹腔注射生理盐水；然后用Morris水迷宫训练方法，比较四组大鼠的空间学习记忆能力的差异；采用放射免疫法测定下丘脑、海马、纹状体和前额皮质每克组织中β内啡肽（β-EP：pendorphin）和强啡肽A（DynA：dynophine草药A）的含量。结果：在Morris水迷宫隐匿平台训练中，有多个时段A组动物的逃避潜伏期较正常对照组C长（P〈0．01或P〈0．05），其中纳洛酮治疗后B组比A组明显缩短（P〈0．05）。大鼠慢性酒精摄入后下丘脑、海马和纹状体内的β-EP水平较正常对照组出现不同程度的升高（P〈0．01或P〈0.05或P〈0．001），而海马、纹状体和前额皮质内的DynA水平却出现下降；而给予纳洛酮处理后，能部分或完全逆转脑区内β-EP和DynA含量的变化并改善大鼠学习记忆的行为学成绩（P〈0．05）。结论：酒精损害了大鼠的学习记忆能力，其机制可能与学习相关脑区内的β-EP和DynA水平的变化有关；纳洛酮逆转其部分脑区内阿片肽水平的变化，从而对学习记忆障碍有一定的改善作用。     

Effect of lead exposure on patterns of food intake in weanling rats

The reduction in growth resulting from lead (Pb) exposure in weanling rats is consistent with a lowering of the biological set-point for food intake. In this study the effects of lead on the patterns of food intake were examined. For 10 days (from ages 26 to 36 days), female rats were provided with drinking water containing 250 ppm lead as the acetate (n = 6) or equivalent acetate as sodium acetate (n = 6). A computerized system was used to monitor daily food intake at 5-min intervals over 10 successive 23-h periods (each period consisting of 12 h dark, 11 h light). Control rats consumed approximately 75% to 85% of their food intake during the dark phase. Exposure to lead resulted in decreased body weight, tail length, and cumulative food intake. Decreased food intake associated with lead during the first 6 days of exposure was due to a decrease in the size of each meal during the dark phase, which reflected a decrease in the duration of each meal. These results suggest that lead, at least initially, was affecting food-satiety signals to produce a premature termination of food intake during a meal. After 6 days, the lead-exposed rats appear to have adjusted their meal size and meal duration to approximately control values. However, this compensation appears to have occurred at the expense of the daily (nocturnal) number of meals, which decreased slightly (although not significantly) in lead-exposed animals. Thus, the total daily intake of food in lead-treated animals remained depressed relative to control animals.     

Beneficial effects of garlic on learning and memory deficits and brain tissue damages induced by lead exposure during juvenile rat growth is comparable to the effect of ascorbic acid

Objective: The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated. Methods: The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead – Ascorbic Acid (Lead-AA), (4) Lead – Garlic (100?mg/kg, daily, gavage) (Lead-Gar). Results: In Morris water maze (MWM), the escape latency and traveled path in the Lead group were significantly higher while, the time spent in the target quadrant (Q1) was lower than Control. Both Lead-Gar and Lead-AA groups spent more times in Q1than to lead group. There were no significant differences in swimming speed between the groups. In passive avoidance (PA) test, the time latency for entering the dark compartment by Lead group was lower than Control. Treatment of the animals by AA and garlic significantly increased the time latency. In Lead group, the total thiol concentration in brain tissues was significantly lower while, MDA was higher than Control. Treatment by both garlic and AA increased total thiol concentrations and decreased MDA. Both garlic and AA decreased the lead content of brain tissues. Conclusion: It is suggested that treatment with garlic attenuates the learning and memory impairments due to lead exposure during juvenile rat growth which is comparable to AA. The possible mechanism may be due to its protective effects against brain tissues oxidative damage as well the lowering effects of brain lead content.     

铅对小鼠学习记忆功能及海马区c-fos表达的影响

目的　观察铅对小鼠海马区c- fos表达及学习记忆功能的影响 ,并探讨二者的关系。方法　小鼠随机分为3个实验组和 1个对照组 ,每组 10只染铅剂量分别为 2 4、4 8和 9 6mmol L ,用跳台学习试验测试小鼠学习记忆能力 ;用RT PCR法观察各组小鼠海马区c fosmRNA的表达状况。结果　 (1) 3个染铅组小鼠跳台学习成绩显著低于对照组 (P <0 . 0 1) ;(2 ) 3个染铅组小鼠c- fosmRNA水平均明显降低 ,以对照组的值为 10 0 ,则低剂量组为 75 . 0 4± 4 .75 ,中剂量组为5 8. 3 5± 5 . 2 9,高剂量组为 42. 66± 6 .3 0 ,与对照组相比 ,P <0 .0 1。高剂量组、中剂量组与低剂量组比较 ,P <0 . 0 1。结论　慢性铅染毒间接阻碍了c- fox基因的反应性表达 ,c- fos基因表达水平的下降可能与铅致小鼠学习记忆功能损害有关。     

The effects of a single exposure to uncontrollable stress on the subsequent conditioned place preference responses to oxycodone,cocaine, and ethanol in rats

Rationale Acute stress has been shown to facilitate the rewarding effects of a number of commonly abused drugs, although the stressor typically must be administered either immediately before or during drug administration and often in the same environment. We have previously reported that a single session of an uncontrollable (inescapable tailshock, IS), but not controllable (escapable tailshock, ES), stressor can enhance the conditioned place preference (CPP) response to morphine, even when stressor and drug administration are separated temporally and spatially. However, this persistent, trans-situational enhancement did not occur to amphetamine CPP. Objectives The following experiments were conducted to determine whether the long-term effects of IS on drug reward are specific to opioids. Materials and methods Adult, male Sprague–Dawley rats were exposed to a single session of IS or remained in their home cages (HC). Twenty-four hours later, using an unbiased procedure, CPP conditioning was conducted with either oxycodone (0, 2, or 5 mg/kg, sc), cocaine (0, 1, 5, or 10 mg/kg, ip), or ethanol (0.3, 1, or 2 g/kg, ip). Another group of rats were exposed to IS, ES, or HC treatment and conditioned with oxycodone (5 mg/kg, sc) 24 h later. Results IS enhanced the subsequent CPP response to oxycodone, but not cocaine or ethanol. This enhancement was dependent on the controllability of the stressor, as ES did not affect oxycodone CPP. Conclusions These results indicate that the long-term, trans-situational enhancing effect of uncontrollable stress on drug reward is specific to opioids. This work was supported by NIH: DA13159, DA015642, and DA16004.     

Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: the role of oxidative stress

The aims of this study were to evaluate whether air pollution during pre-natal and post-natal phases change habituation and short-term discriminative memories and if oxidants are involved in this process. As secondary objectives, it was to evaluate if the change of filtered to nonfiltered environment could protect the cortex of rats against oxidative stress as well as to modify the behavior of these animals. Wistar, male rats were divided into four groups (n?=?12/group): pre and post-natal exposure until adulthood to filtered air (FA); pre-natal period to nonfiltered air (NFA-FA); until (21st post-natal day) and post-natal to filtered air until adulthood (PND21); pre-natal to filtered air until PND21 and post-natal to nonfiltered air until adulthood (FA-NFA); pre and post-natal to nonfiltered air (NFA). After 150 days of air pollution exposure, animals were tested in the spontaneous object recognition test to evaluate short-term discriminative and habituation memories. Rats were euthanized; blood was collected for metal determination; cortex dissected for oxidative stress evaluation. There was a significant increase in malondialdehyde (MDA) levels in the NFA group when compared to other groups (FA: 1.730?±?0.217; NFA-FA: 1.101?±?0.217; FA-NFA: 1.014?±?0.300; NFA: 5.978?±?1.920?nmol MDA/mg total proteins; p?=?0.007). NFA group presented a significant decrease in short-term discriminative (FA: 0.603?±?0.106; NFA-FA: 0.669?±?0.0666; FA-NFA: 0.374?±?0.178; NFA: ?0.00631?±?0.106?sec; p?=?0.006) and an improvement in habituation memories when compared to other groups. Therefore, exposure to air pollution during both those periods impairs short-term discriminative memory and cortical oxidative stress may mediate this process.     

外源性神经节苷脂对铅暴露大鼠学习记忆及海马精氨酸加压素的影响

目的:研究外源性神经节苷脂-1(GM_1)对铅暴露大鼠学习记忆能力及海马细胞精氨酸加压素(AVP)的影响。方法:健康2月龄SD大鼠60只随机分为正常对照组、模型组和GM_1组。正常对照组饮用去离子水,其余2组饮用0.1%醋酸铅去离子水制成慢性染铅大鼠模型。3 mo后,GM_1组腹腔注射GM_1 50 mg·kg~(-1),正常对照组和模型组腹腔注射等量生理盐水,均为14 d。以Y-迷宫试验检测各组大鼠的学习和记忆能力,采用免疫组化的方法测定大鼠海马AVP,并观察其阳性神经元数量的变化。结果:模型组大鼠学习记忆能力较正常对照组明显减低,海马CA_1区AVP阳性神经元数量减少,有统计学意义(P<0.01);GM_1组腹腔注射GM_1后,Y-迷宫错误次数减少,且有统计学意义(P<0.05),其海马CA_1区AVP阳性神经元数量增多,且有统计学意义(P<0.01),CA_3区AVP阳性神经元数量亦增多且有统计学意义(P<0.01)。结论:外源性GM_1可一定程度的改善染铅大鼠的学习记忆能力,可能与海马细胞AVP的阳性表达增强有关。     

The effect of paroxetine,venlafaxine and bupropion administration alone and combined on spatial and aversive memory performance in rats

Background

The use of antidepressants in combination is common practice following non-response to single antidepressant agents. Nevertheless, the scientific literature lacks preclinical studies regarding the combined administration of antidepressants across multiple behavioral measures including, but not limited to, cognition. Hence, we aimed to determine the effects of paroxetine (PAR), venlafaxine (VEN) and bupropion (BUP) alone or combined (PAR + BUP or VEN + BUP) on spatial and affective memory tasks to advance the knowledge about the combined use of antidepressants in cognition.