癫痫持续状态和慢性癫痫对大鼠学习记忆和情感行为的影响

目的探讨急慢性癫痫发作对大鼠认知功能的影响。方法戊四氮(PTZ)诱导大鼠癫痫持续状态(SE)和慢性癫痫(CEP),用交替电刺激Y迷宫试验、Morris水迷宫试验、抬高迷宫试验和旷场试验检测大鼠学习记忆和情感行为变化。结果SE大鼠致痫后近期水迷宫逃避潜伏期延长(P<0.05),平台象限搜寻时间百分比降低(P<0.01),穿越平台区域次数减少(P<0.05)Y迷宫选择错误总数增多(P<0.05);抬高迷宫开放臂中逃避时间延长(P<0.05),进入次数增多(P<0.05);旷场活动的格子数、站立次数及粪便颗粒数均减少(P<0.05)。远期均恢复正常。CEP大鼠致痫后近期水迷宫部分时段逃避潜伏期延长(P<0.05),远期恢复正常,Y迷宫选择错误总数近期和远期均增多(P<0.05)抬高迷宫开放臂中逃避时间和进入次数及旷场活动格子数、站立次数和粪便颗粒数与对照组相比均无明显差别(P>0.05)。结论癫痫持续状态可导致大鼠短期学习记忆功能受损和情感行为异常慢性癫痫引起的学习记忆能力降低持续时间较长,对情感行为无明显影响。交替电刺激Y迷宫在检测癫痫大鼠学习记忆功能方面可能较Morris水迷宫更灵敏。     

γ-氨基丁酸对慢性脑缺血致血管性痴呆大鼠学习记忆能力的影响

目的观察γ-氨基丁酸（GABA）对慢性脑缺血致血管性痴呆（VD）大鼠学习记忆能力及海马CA1区神经元形态学的影响。方法将SD大鼠随机分为假手术组、模型组、GABA组,采用双侧颈总动脉永久性结扎法建立VD模型。GABA组术后腹腔注射GABA0.5g.kg-1.d-1,连续注射60d;用Morris水迷宫实验检测大鼠空间学习记忆能力;Nissl染色观察大鼠海马CA1区神经元形态学变化。结果 GABA能明显改善VD大鼠学习记忆能力,也能减轻海马CA1区神经元损伤。结论 GABA能改善慢性脑缺血致VD大鼠的学习记忆能力,减轻海马神经元损伤可能是其机制之一。     

Functional convergence of developmentally and adult‐generated granule cells in dentate gyrus circuits supporting hippocampus‐dependent memory

In the hippocampus, the production of dentate granule cells (DGCs) persists into adulthood. As adult‐generated neurons are thought to contribute to hippocampal memory processing, promoting adult neurogenesis therefore offers the potential for restoring mnemonic function in the aged or diseased brain. Within this regenerative context, one key issue is whether developmentally generated and adult‐generated DGCs represent functionally equivalent or distinct neuronal populations. To address this, we labeled separate cohorts of developmentally generated and adult‐generated DGCs and used immunohistochemical approaches to compare their integration into circuits supporting hippocampus‐dependent memory in intact mice. First, in the water maze task, rates of integration of adult‐generated DGCs were regulated by maturation, with maximal integration not occurring until DGCs were five or more weeks in age. Second, these rates of integration were equivalent for embryonically, postnatally, and adult‐generated DGCs. Third, these findings generalized to another hippocampus‐dependent task, contextual fear conditioning. Together, these experiments indicate that developmentally generated and adult‐generated DGCs are integrated into hippocampal memory networks at similar rates, and suggest a functional equivalence between DGCs generated at different developmental stages. © 2010 Wiley Periodicals, Inc.     

Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition

We found that a short exercise period enhanced cognitive function on the Morris water maze (MWM), such that exercised animals were significantly better than sedentary controls at learning and recalling the location of the platform. The finding that exercise increased brain-derived neurotrophic factor (BDNF), a molecule important for synaptic plasticity and learning and memory, impelled us to examine whether a BDNF-mediated mechanism subserves the capacity of exercise to improve hippocampal-dependent learning. A specific immunoadhesin chimera (TrkB-IgG), that mimics the BDNF receptor, TrkB, to selectively bind BDNF molecules, was used to block BDNF in the hippocampus during a 1-week voluntary exercise period. After this, a 2-trial-per-day MWM was performed for 5 consecutive days, succeeded by a probe trial 2 days later. By inhibiting BDNF action we blocked the benefit of exercise on cognitive function, such that the learning and recall abilities of exercising animals receiving the BDNF blocker were reduced to sedentary control levels. Inhibiting BDNF action also blocked the effect of exercise on downstream systems regulated by BDNF and important for synaptic plasticity, cAMP response-element-binding protein (CREB) and synapsin I. Specific to exercise, we found an association between CREB and BDNF expression and cognitive function, such that animals who were the fastest learners and had the best recall showed the highest expression of BDNF and associated CREB mRNA levels. These findings suggest a functional role for CREB under the control of BDNF in mediating the exercise-induced enhancement in learning and memory. Our results indicate that synapsin I might also contribute to this BDNF-mediated mechanism.     

PKA-CREB信号转导通路在大鼠慢性脑缺血所致认知功能障碍中的作用

目的:观察PKA-CREB信号转导通路在慢性脑缺血所致大鼠认知功能损害中的作用。方法:结扎大鼠双侧颈总动脉,制成慢性脑缺血模型,分缺血8周组和假手术对照组,术后第8周时用Morris水迷宫测定大鼠学习记忆能力。用Westernbloting检测大鼠海马胞核内PKAca及pCREB的表达。结果:缺血组与假手术组相比学习记忆能力明显下降(P<0.05),缺血组大鼠海马中PKAca及pCREB的表达与假手术组相比也下降(P<0.05),且两者之间的下降存在正相关关系。结论:PKA-CREB信号转导通路可能参与了慢性脑缺血所致大鼠认知功能的损害。     

影响小鼠Morris水迷宫成绩的因素探讨及改进措施

Morris水迷宫自英国心理学家Richard Morris于1981年首次使用以来,已成为一种研究与海马功能直接相关的空间学习记忆机制的标准模式,能较准确地反映动物的空间参考记忆能力[1].Morris水迷宫能为考察实验动物空间认知能力提供较多的评价指标,全面记录其认知加工过程,客观地反映其认知水平.但是,Morris水迷宫的实施过程中还有很多影响其准确性和可靠性的因素存在,如实验动物的选择、实验设计、实验的实施过程等.因此,笔者现就影响小鼠Morris水迷宫成绩的若干因素(Morris水迷宫自身因素及小鼠主观因素等)进行综述,以期为实验工作者们减少误差提供一些帮助.     

Developmental 3,4-methylenedioxymethamphetamine (MDMA) impairs sequential and spatial but not cued learning independent of growth,litter effects or injection stress

Previously, we have shown that rats administered MDMA from postnatal (P) days 11-20 had reductions in body weight during the period of treatment and as adults they had deficits in sequential and spatial learning and memory. In the present study, to control for weight reductions, we used litters with double the number of offspring to induce growth restriction comparable to that of standard size litters treated with MDMA. Litters were treated twice daily from P11 to 20 with vehicle or MDMA (20 mg/kg) or only weighed. Males, but not females, exposed to MDMA had longer latencies and more errors in the Cincinnati water maze compared to males of the other treatments. In the Morris water maze (210 cm pool, 10x10 cm platform), the MDMA animals were impaired relative to all other treatments during acquisition. Only the MDMA females showed deficits when the platform was shifted to a new location, however, both MDMA males and females were impaired when the location of the platform was again shifted and a reduced platform (5x5 cm) used. No differences were observed in the ability to swim a straight channel, locate a platform with a cue, or the endocrine response to forced swim among the treatment groups. No differences were seen between animals injected with saline and those only weighed. The data suggest that factors, such as growth retardation, multiple injections, or the composition of the litter, do not affect the development of learning and memory impairments resulting from P11 to 20 MDMA exposure. The large litter approach offers a novel method to control for undernutrition during the preweaning period in rodents.     

抗癫痫药物对大鼠记忆和学习功能影响的研究

目的探讨抗癫痫药物对大鼠认知功能的影响。方法健康雄性性成熟SD大鼠70只,随机分为正常对照组(NS组)、癫痫对照组(PTZ组)、卡马西平(CBZ)组、苯妥英钠(PHT)组、丙戊酸钠(VPA)组、妥泰(TPM)组及拉莫三嗪(LTG)组,每组10只。除NS组外其他6组用PTZ点燃。抗癫痫治疗2周后用Morris水迷宫测试认知功能。采用方差分析进行统计学处理。结果PTZ组学习成绩提高快(P<0.05,P<0.01)。卡马西平组、丙戊酸钠组、拉莫三嗪组测试成绩捉高很快(P<0.01),优于NS组。苯妥英钠组测试成绩提高较慢(P<0.05),与NS组比较无明显差异。妥泰组测试成绩提高慢,各次、各天之间差异无显著性(P>0.05),较NS组差。在寻找平台象限和在平台象限逗留时间的测试中,妥泰寻找时间最长,逗留时间最短,两项成绩均低于其他组(P<0.05,P<0.01);其他各组之间差异无显著性。结论PHT可能损害大鼠的学习、判断功能,TPM还可损害大鼠的记忆功能。     

Impaired learning and memory performance in a subclinical hypothyroidism rat model induced by hemi-thyroid electrocauterisation

It is well known that clinical hypothyroidism (CH) can induce cognitive deficits, and the decision to start treatment for CH with thyroxine is usually straightforward. However, the relationship of cognition dysfunction with subclinical hypothyroidism (SCH) is inconsistent, and the decision concerning the need to treat SCH is controversial. In the present study, we induced a SCH rat model by hemi-thyroid electrocauterisation; then employed a serial of behavioural tests, including a beam balance, open field task and Morris water maze (MWM), to investigate the behaviour performance of SCH rats; and finally explored the protein expression of phosphorylated extracellular signal-regulated kinase (ERK)1/2 in the hippocampus by western blotting. The results demonstrated that hemi-thyroid electrocauterised rats had an elevated plasma thyrotrophin-stimulating hormone (TSH) level, with normal free thyroxine (fT4) and triiodothyronine (T3) concentrations, which defines SCH in humans. If rat SCH is diagnosed according to measurements of both plasma TSH higher than 97.5 percentile for the sham group and fT4 in the range 2.5-97.5 percentile for the sham group, the success rate of SCH modelling was 66.6%. SCH decreased exploratory behaviour but did not affect motor function in rats, showing a negative correlation of exploratory behaviour with plasma TSH concentration. Moreover, SCH rats displayed an impairment of learning and memory ability in the MWM task, with a longer escape latency in the acquisition phase and a shorter duration in the target quadrant in the test phase compared to that of sham rats. The mechanism for this might be related to the increased plasma TSH concentration, the decreased hippocampal T3 level and the enhanced expression of phosphorylated ERK1/2 in the hippocampus. The results of the present study, together with the results obtained in other studies, suggest that treatment is necessary for SCH.     

纳洛酮改善东莨菪碱所致大鼠空间工作记忆障碍的神经机制研究

目的　对纳洛酮改善东莨菪碱所致大鼠空间工作记忆障碍的神经机制进行探索。目的　对纳洛酮改善东莨菪碱所致大鼠空间工作记忆障碍的神经机制进行探索。方法　大鼠随机分成三组:正常组、东莨菪碱组和纳洛酮治疗组,采用Morris水迷宫延缓性匹配任务试验记录每只大鼠前后两次逃避潜伏期的时间。利用免疫组化及图像分析技术,定量测定各组大鼠海马和前额叶皮层胆碱乙酰转移酶(ChAT)合成,利用电子显微镜技术,观察大鼠海马CA1区超微结构的改变。结果　(1)前后两次逃避潜伏期在正常组呈极显著性差异(t =7.32, P =0.00),东莨菪碱组无差异 (t =1.01, P =0.35),纳洛酮治疗组呈显著性差异(t =3.19, P =0.02)。(2)各组大鼠海马CA1、CA3区, 前额叶皮层神经元ChAT量无差别(P >0.05)。(3)各组大鼠锥体细胞胞体超微结构正常,但东莨菪碱组CA1区神经元突触超微结构明显改变。结论　M-型胆碱能受体阻滞剂东莨菪碱能损害大鼠空间工作记忆;阿片受体阻滞剂纳洛酮能够改善这种损害,其神经机制并非是增加 ChAT活性,而是能促进神经元突触囊泡Ach向突触间隙大量释放,及增加突触后致密物质密度。     

代谢型谷氨酸受体激动剂3,5-二羟基苯甘氨酸对大鼠学习记忆行为的影响

目的研究代谢型谷氨酸受体激动剂3,5-二羟基苯甘氨酸(DHPG)对SD大鼠学习记忆行为的影响。方法选用雄性SD大鼠,随机分为DHPG组和人工脑脊液(ACSF)组,利用大鼠脑立体定位方法分别于两侧海马CA1区微量注射DHPG和ACSF。应用Morris水迷宫进行定位航行实验和空间探索实验测定两组大鼠DHPG和ACSF注射前后的学习记忆能力。结果 DHPG组海马CA1区注射DHPG后,与ACSF组比较,大鼠定位航行实验中逃避潜伏期延长(P0.05);空间探索实验中穿越原平台次数、目标象限路程均减少(P0.05)。结论 DHPG可能与大鼠学习记忆障碍有关。     

Applications of the Morris water maze in the study of learning and memory

The Morris water maze (MWM) was described 20 years ago as a device to investigate spatial learning and memory in laboratory rats. In the meanwhile, it has become one of the most frequently used laboratory tools in behavioral neuroscience. Many methodological variations of the MWM task have been and are being used by research groups in many different applications. However, researchers have become increasingly aware that MWM performance is influenced by factors such as apparatus or training procedure as well as by the characteristics of the experimental animals (sex, species/strain, age, nutritional state, exposure to stress or infection). Lesions in distinct brain regions like hippocampus, striatum, basal forebrain, cerebellum and cerebral cortex were shown to impair MWM performance, but disconnecting rather than destroying brain regions relevant for spatial learning may impair MWM performance as well. Spatial learning in general and MWM performance in particular appear to depend upon the coordinated action of different brain regions and neurotransmitter systems constituting a functionally integrated neural network. Finally, the MWM task has often been used in the validation of rodent models for neurocognitive disorders and the evaluation of possible neurocognitive treatments. Through its many applications, MWM testing gained a position at the very core of contemporary neuroscience research.     

Zinc transporter-3 expression and long-term cognitive impairments in a rat model of neonatal concurrent seizure

BACKGROUND： Developmental seizures, which are pathologically characterized by regenerative sprouting of hippocampal mossy fibers, cause long-term damaging effects to synaptic plasticity. Zn^2＋ metabolism has been shown to contribute to the regenerative sprouting of hippocampal mossy fibers Furthermore, zinc transporter-3 （ZnT3） is responsible for Zn^2＋ transport in the hippocampal mossy fiber pathway. OBJECTIVE： To investigate the effects of long-term recurrent neonatal seizures on learning, memory formation and hippocampal ZnT3 expression in rats. DESIGN, TIME AND SETTING： Based on molecular biological research and behavioral examination a randomized, controlled, animal experiment was performed at the Laboratory Animal Center, Peking University Health Science Center, between October 2004 and July 2005. MATERIALS： Flurothyl was purchased from Aldrich Chemical Co., USA. ZnT3 mRNA in situ hybridization kits were provided by Tianjin Haoyang Biological Manufacture Co., Ltd., China. Morris water maze was produced by Shanghai Jiliang Science and Technology Co., Ltd., China. METHODS： Sixty, 6-day old, Wistar rats were randomly divided into three groups： single seizure （n = 21）, recurrent seizure （n = 21, one seizure daily for 6 consecutive days）, and control （n = 18）. Seizures were induced by flurothyl gas inhalation, in the single seizure and recurrent seizure groups. MAIN OUTCOME MEASURES： At postnatal days 12, 46 and 90, rat hippocampal ZnT3 mRNA expression was detected by RT-PCR; at postnatal days 46 and 90, ZnT3 mRNA expression was determined by in situ hybridization; and at postnatal days 41-46 and 85 90, rat spatial learning and memory formation were examined by the Morris water maze test. RESULTS： RT-PCR results revealed that at postnatal day 12, ZnT3 expression was significantly greater in the recurrent seizure group than in the control and single seizure groups, and at day 46, it was also significantly greater in the recurrent seizure group compared with the control group （P 〈 0.05）. In situ hybridization results showed that at postnatal day 46, the recurrent seizure group exhibited increased hippocampal ZnT3 expression over the control and single seizure groups （P〈0.05）. Morris water maze test results displayed that, in the first place navigation test at postnatal day 44, and the second test at days 87-88, the recurrent seizure group exhibited significantly higher value of average escape latency compared with the control group （P 〈 0.05）. In the two spatial probe tests, the search strategies were significantly inferior in the recurrent seizure group than in the control and single seizure groups （P 〈 0.05）. CONCLUSION： Neonatal concurrent seizures produce long-term damaging effects on hippocampal ZnT3 expression and cognitive function, while both of which have no parallel correlation.     

慢性脑缺血海马CA1区HCN1蛋白表达下调与学习记忆损伤研究

目的 探讨慢性脑缺血导致大鼠认知功能障碍与HCN1通道亚型蛋白表达变化的内在关系。方法 健康成年雄性SD大鼠20只,随机分为假手术组、缺血组,每组各10只。各组缺血4周后采用Morris水迷宫检测大鼠学习记忆功能,免疫组化检测HCN1表达水平,进一步用蛋白印迹检测HCN1蛋白表达水平。结果 与假手术组相比,缺血组大鼠逃避潜伏期明显延长(P<0.05); 缺血组大鼠海马CA1区HCN1蛋白表达水平明显降低,与模型组比较有明显差异(P<0.05)。结论 慢性脑缺血海马CA1区存在HCN1通道亚型表达下调且参与大鼠认知功能损伤,可能为治疗慢性脑缺血所致认知功能障碍的新靶点。     

3,4-Methylenedioxymethamphetamine in adult rats produces deficits in path integration and spatial reference memory.

BACKGROUND: +/-3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that causes cognitive deficits in humans. A rat model for learning and memory deficits has not been established, although some cognitive deficits have been reported. METHODS: Male Sprague-Dawley rats were treated with MDMA (15 mg/kg x 4 doses) or saline (SAL) (n = 20/treatment group) and tested in different learning paradigms: 1) path integration in the Cincinnati water maze (CWM), 2) spatial learning in the Morris water maze (MWM), and 3) novel object recognition (NOR). One week after drug administration, testing began in the CWM, then four phases of MWM, and finally NOR. Following behavioral testing, monoamine levels were assessed. RESULTS: +/-3,4-Methylenedioxymethamphetamine-treated rats committed more CWM errors than did SAL-treated rats. +/-3,4-Methylenedioxymethamphetamine-treated animals were further from the former platform position during each 30-second MWM probe trial but showed no differences during learning trials with the platform present. There were no group differences in NOR. +/-3,4-Methylenedioxymethamphetamine depleted serotonin in all brain regions and dopamine in the striatum. CONCLUSIONS: +/-3,4-Methylenedioxymethamphetamine produced MWM reference memory deficits even after complex learning in the CWM, where deficits in path integration learning occurred. Assessment of path integration may provide a sensitive index of MDMA-induced learning deficits.     

Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats

Brain-derived neurotrophic factor (BDNF) is abundantly expressed in the hippocampus and cerebral cortex and is involved in synaptic plasticity and long-term potentiation (LTP). The present study was under taken to investigate whether endogenous BDNF was required for spatial learning and memory in a rat model. Antibodies to BDNF (anti-BDNF, n=7) or control immunoglobulin G (control, n=6) were delivered into the rat brain continuously for 7 days with an osmotic pump. The rats were then subjected to a battery of behavioral tests. The results show that the average escape latencies in the BDNF antibody treated group were dramatically longer than those of the control (F=13.3, p<0.001). The rats treated with control IgG swam for a significantly longer distance in the P quadrant (where the escape plane had been placed) compared with the other three quadrants (p<0.05). In contrast, anti-BDNF-treated rats swam an equivalent distance in all four quadrants. The average percentage of swimming distance in the P quadrant by anti-BDNF-treated rats was much less than that by control IgG treated rats (p<0.001). These results suggest that endogenous BDNF is required for spatial learning and memory in adult rats.     

Melatonin mitigates hippocampal and cognitive impairments caused by prenatal irradiation

Formation of new neurons and glial cells in the brain is taking place in mammals not only during prenatal embryogenesis but also during adult life. As an enhancer of oxidative stress, ionizing radiation represents a potent inhibitor of neurogenesis and gliogenesis in the brain. It is known that the pineal hormone melatonin is a potent free radical scavenger and counteracts inflammation and apoptosis in brain injuries. The aim of our study was to establish the effects of melatonin on cells in the hippocampus and selected forms of behaviour in prenatally irradiated rats. The male progeny of irradiated (1 Gy of gamma rays; n = 38) and sham‐irradiated mothers (n = 19), aged 3 weeks or 2 months, were used in the experiment. Melatonin was administered daily in drinking water (4 mg/kg b. w.) to a subset of animals from each age group. Prenatal irradiation markedly suppressed proliferative activity in the dentate gyrus in both age groups. Melatonin significantly increased the number of proliferative BrdU‐positive cells in hilus of young irradiated animals, and the number of mature NeuN‐positive neurons in hilus and granular cell layer of the dentate gyrus in these rats and in CA1 region of adult irradiated rats. Moreover, melatonin significantly improved the spatial memory impaired by irradiation, assessed in Morris water maze. A significant correlation between the number of proliferative cells and cognitive performances was found, too. Our study indicates that melatonin may decrease the loss of hippocampal neurons in the CA1 region and improve cognitive abilities after irradiation.     

Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring

Clinical studies demonstrate that prenatal stress causes cognitive deficits and increases vulnerability to affective disorders in children and adolescents. The underlying mechanisms are not yet fully understood. Here, we reported that prenatal stress (10 unpredictable, 1 s, 0.8 mA foot shocks per day during gestational days 13-19) impaired long-term potentiation (LTP) but facilitated long-term depression (LTD) in hippocampal CA1 region in slices of the prenatal stressed offspring (5 weeks old). Cross-fostering neonate offspring by the prenatal stressed or control mothers did not change the effects of prenatal stress on the hippocampal LTP and LTD. Furthermore, prenatal stress enhanced the effects of acute stress on the hippocampal LTP and LTD and impaired spatial learning and memory in the Morris water maze in the young rat offspring. Therefore, prenatal stress alters synaptic plasticity and enhances the effects of acute stress on synaptic plasticity in the hippocampus, which may be the mechanism for the impaired spatial learning and memory in young rat offspring.     

Effect of reversible inactivation of the supramammillary nucleus on spatial learning and memory in rats

Memory includes processes such as acquisition, consolidation and retrieval. Reference memory (RM) and working memory (WM) are two kinds of memory that can be assessed in rodents using spatial tasks, especially using the Morris water maze. The Morris water maze is particularly sensitive to hippocampal lesions. The supramammillary nucleus (SuM) has strong links with the hippocampus and septum. The role of the SuM on spatial learning is controversial. In the present study, involvement of SuM in the different steps of spatial RM and WM was investigated in the Morris water maze using reversible inactivation of SuM with lidocaine. Lidocaine (0.5 microl, 4%) was injected into the SuM through a guide cannula implanted above the SuM. The rats were trained on RM and WM versions of the Morris water maze. SuM was inactivated before training or immediately after training or before the probe trial of retrieval tests. Reversible inactivation of the SuM impaired consolidation of RM, and of consolidation and retrieval of WM. Therefore, it seems that activity of SuM neurons plays a role in spatial RM and WM learning and memory in the rat.     

Baclofen infused in rat hippocampal formation impairs spatial learning

Recent studies show that baclofen, a selective GABA_B agonist, impairs different kinds of learning. In the present study we investigated the effect of microinfused baclofen into the hippocampus of male Wistar rats, on the performance in the Morris water maze. Rats of 8–10 weeks of age were implanted with cannulae aimed bilaterally at the hippocampal formation. Baclofen (1 μl of 0.2 mM, 2.0 mM, and 20.0 mM) or sterilized saline was microinfused 1 h before each daily session (3 trials/session, 1 session/day) for 4 days. On the fifth day, the animals did not receive drug or saline injections and the retention of the location of the escape platform was tested in a 30 s free swim trial. Results from the free swim trial indicate that the doses of baclofen used during training affected the ability of the rats to swim to the target quadrant. Although no significant difference compared with the saline group was observed, the experimental rats showed a more generalized swim trajectory in the area of the target and both adjacent quadrants. Moreover, 1μl of 20.0 mM baclofen also impaired the acquisition. We suggest that baclofen has an impairing action on spatial learning, although more studies should be conducted to reach a more precise conclusion. Hippocampus 1998;8:109–113. © 1998 Wiley-Liss, Inc.