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.     

Effects of scopolamine on acquisition of passive avoidance

Summary Scopolamine was tested for effects on acquisition of a passive-avoidance problem. First mice were given four trials 24 hours apart on a step-off apparatus. Various dose levels of the drug were studied. For one group the drug was injected i.p. 20 minutes prior to each trial, in the other immediately after. Doses of 5.0 mg/kg and higher greatly interfered with the acquisition of the response, but only when injected prior to the trial. These results failed to indicate any direct effect of the drug on the learning process. The only time the drug affected the behavior was when the animal was under its influence at the time of testing.A second experiment was conducted in which mice were trained as before but pre-injection of 5.0 mg/kg of scopolamine was used. However, the mice were injected with the drug on only some of the trials. In all, six groups were studied, and their performance compared with a group that had received scopolamine on all trials and with one that received saline on all trials. When the data were examined for evidence of dissociation, it was clear that it was not present. Further analysis showed that animals which had learned, as indicated by their performance on the early trials conducted when they were not drugged, failed to show evidence of memory when given additional trials after being drugged. This outcome clearly indicated that a major effect of scopolamine was on the performance of the animal. Also, animals which had received 1 or 2 trials while drugged and given additional trials in the nondrugged state, showed a rapid increase in latency on succeeding trials equal that of animals which had not been drugged at all.These results, in light of other research, indicate that the effect of scopolamine on this type of learning task does not appear to be through a modification of the consolidation process.A preliminary report of Experiment I was made at the Southeastern Psychological Association Annual Meeting in Atlanta, Georgia, April, 1967. Supported by NIMH Grant No. MH 12770-01 to the senior author.     

The seed extract of Cassia obtusifolia ameliorates learning and memory impairments induced by scopolamine or transient cerebral hypoperfusion in mice

In the present study, we assessed the effect of the ethanolic extract of the seeds of Cassia obtusifolia (COE) on the learning and memory impairments induced by scopolamine or transient bilateral common carotid artery occlusion (2VO). In a study of the cholinergic dysfunction induced by scopolamine, single COE (25, 50, or 100 mg/kg, p.o.) administration significantly attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks (P<0.05) and also reduced escape-latency on the Morris water maze task (P<0.05). In the 2VO study, COE (50 mg/kg, p.o.) significantly reversed 2VO-induced cognitive impairments in mice by the passive avoidance and the Y-maze tasks (P<0.05). Moreover, COE (50 mg/kg, p.o.) also reduced escape-latency and prolonged swimming time in the target quadrant during a probe trial of the Morris water maze task (P<0.05). In an in vitro study, COE was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50) value: 81.6 microg/ml). Furthermore, COE also inhibited acetylcholinesterase activity in an ex vivo study. These results suggest that COE attenuates memory impairment induced by scopolamine or 2VO and that these effects are mediated by enhancing the cholinergic nervous system via acetylcholinesterase inhibition.     

Beneficial effects of resveratrol on scopolamine but not mecamylamine induced memory impairment in the passive avoidance and Morris water maze tests in rats

Resveratrol (3,5,4-trihydroxy-trans-stilbene), which is found in grapes and red wine has been shown to protect neuronal cells with its antioxidant activity, improve memory function in dementia and reverse acetylcholine esterase (AChE) activity. The aim of this study was to investigate the effect of resveratrol on emotional and spatial memory in naive rats, as well as on scopolamine- and mecamylamine-induced memory impairment in the passive avoidance and Morris water maze (MWM) tests. Resveratrol (12.5, 25 and 50 mg/kg), scopolamine (0.6 mg/kg) and mecamylamine (10 mg/kg) were administered to male Wistar rats. In the passive avoidance test, there was no significant difference in the first day latency between all groups, whereas scopolamine and mecamylamine significantly shortened the second day latency compared to the control group. Resveratrol reversed the effect of scopolamine at all doses used, but it had no effect on mecamylamine-induced memory impairment in the passive avoidance test. Both scopolamine and mecamylamine significantly decreased the time spent in the escape platform quadrant during the probe trial of the MWM test compared to the control group. Resveratrol reversed the effect of scopolamine at all doses, but did not change the effect of mecamylamine in the MWM test. There were no significant differences in the locomotor activities of any of the groups. In conclusion, we suggested that resveratrol had improving effects on learning and memory by acting on muscarinic cholinergic receptors and at least in part, may reverse AChE activity.     

Some effects of scopolamine on a passive avoidance response in rats

Summary Results are reported for the effects of scopolamine and methscopolamine on a passive avoidance response in rats. Scopolamine in adequate doses severely disrupted both the acquisition and the retention of this response. Since methscopolamine was without effect, it was concluded that the site of action is in the central nervous system.It was found that the retention deficit cannot be attributed to dissociation and, surprisingly, that rats trained and injected with scopolamine on two consecutive days perform as well as normal controls on the second day. The possibility that this latter effect was due to tolerance found no experimental support.These results seem to suggest that scopolamine can produce response disinhibition. A neuronal hypothesis and a possible site of action for scopolamine were proposed to explain the behavioral data.This work was supported by Research Grant MH 08486-01 from the National Institute of Mental Health, United States Public Health Service. The author gratefully acknowledges the assistance of Allan Krebs who ran some of the animals in Experiments I and II and of Howard Moltz who made many helpful suggestions regarding a draft of this paper.     

The effect of para-chlorophenylalanine and scopolamine on passive avoidance in chicks

Four-day-old Vantress x Arbor Acre chicks were treated for key-peck passive avoidance (PA) learning following intraperitoneal injections of parachlorophenylalanine (PCPA) and/or scopolamine. In Experiment 1, chicks were pre-treated with either three or five injections of PCPA (150 mg/kg) or saline across th first three posthatch days and then tested for PA learning on the fourth posthatch day. In Experiment 2, chicks were first pre-treated with three injections of PCPA (150 mg/kg) or saline, and then injected with either scopolamine (0.5 mg/kg) or saline 20 min prior to PA testing on the fourth posthatch day. Major findings were: (a) Chicks pre-treated with PCPA did not significantly differ from saline control chicks in either the acquisition or maintenance of response suppression during PA testing; (b) chicks injected with scopolamine were significantly disrupted in PA learning as compared to saline control chicks; and (c) PCPA pre-treatment did not significantly affect the scopolamine-induced disruption of PA learning. These findings, therefore, suggest that cholinergic, but not serotonergic, mechanisms are involved in PA learning of the young chick.     

孕酮和孕烯醇酮硫酸盐对东莨菪碱引起的小鼠记忆损伤的保护作用

目的 :观察孕酮和孕烯醇酮硫酸盐对东莨菪碱引起的小鼠记忆损伤的保护作用。方法 :用东莨菪碱造成小鼠记忆损伤的模型 ,应用被动避暗试验测定潜伏期以评价记忆成绩。结果 :小鼠给予东莨菪碱 (1mg·kg-1,ip)后 ,其潜伏期显著减少 ,表明造成了明显的记忆损伤。孕酮 (1,10mg·kg-1,sc)和孕烯醇酮硫酸盐 (1mg·kg-1,sc)均可以在被动避暗试验中减轻东莨菪碱引起的记忆损伤。结论 :孕酮和孕烯醇酮硫酸盐可改善记忆损伤。     

孟鲁司特对东莨菪碱模型小鼠学习记忆及脑内胆碱能神经的影响

目的：研究孟鲁司特（Mon）对东莨菪碱（Scop）致痴呆模型小鼠学习记忆及脑内胆碱能神经的影响。方法：将动物按体重随机分为5组,正常对照组[溶媒（Veh）＋Veh]、阴性对照组（Scop＋Veh）、阳性对照组[Scop＋多奈哌齐（Done）2．0mg／kg]、低剂量孟鲁司特组（Scop＋Mon 1.0mg／kg）、高剂量孟鲁司特组（Scop＋Mon2．0mg／kg）。灌胃给药,除正常对照组腹腔注射生理盐水外,其他各组小鼠给药前30min腹腔注射东莨菪碱（1．0mg·kg^-1·d^-1）,连续给药14d后采用Morris水迷宫和Y迷宫实验测定学习记忆功能,并测定脑海马及皮层乙酰胆碱（ACh）水平及乙酰胆碱酯酶（TChE）的活性。结果：与阴性对照组相比,孟鲁司特（1．0、2．0mg·kg^-1·d^-1）能显著缩短Morris水迷宫隐藏平台训练的潜伏期,增加动物在空间探索实验中对目标象限的搜索时间及原平台所在位置的穿越次数,增加Y迷宫实验中正确反应次数。孟鲁司特还能显著降低小鼠海马及皮层乙酰胆碱酯酶活性,增加乙酰胆碱含量。结论：孟鲁司特通过抑制东莨菪碱所致的痴呆小鼠脑内乙酰胆碱酯酶活性增加乙酰胆碱含量,继而改善小鼠学习记忆损害。     

Cycloheximide and passive avoidance memory in mice: Time-response,dose-response and short-term memory

The greatest loss of memory shown by mice 24 hr after learning was found to occur with cycloheximide (CXM) (120 mg/kg) administered subcutaneously 30 min before training. With injection at this time the extent of the amnesia was done dependent (30–150 mg/kg) and the resultant amnesia was found to be relatively constant when tested at 1, 7 or 14 days. An attempt was made to follow the development of this amnesia with 100 and 120 mg/kg CXM. However, the saline controls showed an unexpectedly low avoidance 6 hr after training. This was interpreted as a possible interaction between the stress of the injection and the 6 hr interval. An experiment designed to test this possibility showed that mice injected with 0.1 ml of 1% lignocaine gave high avoidance at 6 hr but mice receiving only a needle puncture of the skin gave performances similar to mice receiving saline injections. It was felt that these findings cast doubt on the usefulness of the passive avoidance task in the assessment of drug action on short term memory.     

A synthetic retinoid Am80 (tamibarotene) rescues the memory deficit caused by scopolamine in a passive avoidance paradigm

Memory deficit in rats treated with scopolamine was rescued by several synthetic retinoids, RAR-ligands (Am80, Am555S, Tp80) and an RXR-ligand (HX630). These results may have implications for the treatment of Alzheimer's disease, age-related dementia, Parkinson's disease, and other neurological disorders.     

Influence of ATP-sensitive potassium channels on lithium state-dependent memory of passive avoidance in mice

The effects of ATP-sensitive potassium channels on lithium induced state-dependent memory of passive avoidance task were examined in mice. The pre-training (5 mg/kg) and pre-test (5 mg/kg) injection of lithium impaired memory retrieval on the test day. Impairment of pre-training lithium was restored by pre-test administration of lithium (5 mg/kg), diazoxide, an ATP-sensitive potassium channel opener, (15, 30 and 60 mg/kg) or glibenclamide, an ATP-sensitive potassium channel blocker, (6 and 18 mg/kg). Pre-test administration of inactive doses of lithium (2.5 and 10 mg/kg) plus lower and inactive dose of glibenclamide (2 mg/kg) or diazoxide (1.5 mg/kg) also reversed the amnesia induced by pre-training lithium (5 mg/kg). In conclusion, the ATP-sensitive potassium channel opener or blocker not only mimicked the effect of lithium in state-dependent learning in the absence of lithium on the test day, but also potentiated the effect of low dose of lithium in restoration of memory. Therefore, ATP-sensitive potassium channels may have a modulatory influence on lithium response.     

Effects of endogenous morphine deprivation on memory retention of passive avoidance learning in mice

Memory and the processes of learning in mammals are well known to be affected by opioid agonists such as morphine, which has been proven to interfere and cause amnesia. The presence of endogenous morphine has been demonstrated in various tissues from mammals to invertebrates. In this study, we have investigated the effects caused by in-vivo immunodepletion of endogenous morphine on working memory under different experimental conditions. When mice were submitted to fasting, a stress condition, acquisition and consolidation of memory were significantly impaired compared to controls. This was demonstrated by a decrease in entry latency into the dark room in the retention session of the passive avoidance test. This effect was significantly reversed to baseline values when endogenous morphine was depleted from the extracellular brain space. These findings support a role for endogenous morphine in weakening memory processes under stress conditions.     

百两茶提取物对东莨菪碱诱导小鼠学习记忆障碍的影响

目的研究百两茶提取物对东莨菪碱诱导小鼠学习记忆障碍的影响。方法雄性BALB/C小鼠60只,随机分为6组,分别为空白对照组,东莨菪碱模型组,石杉碱甲片组,百两茶提取物低、中、高(100、200、400 mg·kg-1)剂量组,各组连续给药28 d,于试验前4 d除空白对照组外其余各组小鼠腹腔注射东莨菪碱2 mg·kg-1建立小鼠记忆障碍模型,随后进行跳台试验,记录跳下平台的潜伏期,进行水迷宫测试,记录动物5 min内登台时间。测试毕,处死小鼠,分离大脑皮质和海马,匀浆取上清液测大脑皮质和海马中超氧化物歧化酶(SOD)和乙酰胆碱酯酶(Ach E)的含量。结果百两茶提取物高剂量(400 mg·kg-1)能明显增加小鼠跳台潜伏期(P<0.05),缩短水迷宫小鼠登台时间(P<0.05),升高小鼠大脑皮质和海马组织SOD含量和抑制ACh E的活性。结论百两茶提取物具有明显改善学习记忆作用。     

Nociceptin/orphanin FQ and nocistatin on learning and memory impairment induced by scopolamine in mice.

1. Nociceptin, also known as orphanin FQ, is an endogenous ligand for the orphan opioid receptor-like receptor 1 (ORL1) and involves in various functions in the central nervous system (CNS). On the other hand, nocistatin is recently isolated from the same precursor as nociceptin and blocks nociceptin-induced allodynia and hyperalgesia. 2. Although ORL1 receptors which display a high degree of sequence homology with classical opioid receptors are abundant in the hippocampus, little is known regarding their role in learning and memory. 3. The present study was designed to investigate whether nociceptin/orphanin FQ and nocistatin could modulate impairment of learning and memory induced by scopolamine, a muscarinic cholinergic receptor antagonist, using spontaneous alternation of Y-maze and step-down type passive avoidance tasks in mice. 4. While nocistatin (0.5-5.0 nmol mouse-1, i.c.v.) administered 30 min before spontaneous alternation performance or the training session of the passive avoidance task, had no effect on spontaneous alternation or passive avoidance behaviours, a lower per cent alternation and shorter median step-down latency in the retention test were obtained in nociceptin (1.5 and/or 5.0 nmol mouse-1, i.c.v.)-treated normal mice. 5. Administration of nocistatin (1.5 and/or 5.0 nmol mouse-1, i.c.v.) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, attenuated the scopolamine-induced impairment of spontaneous alternation and passive avoidance behaviours. 6. These results indicated that nocistatin, a new biologically active peptide, ameliorates impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that these peptides play opposite roles in learning and memory.     

Comparative study of retrograde amnesia in rats on active and passive avoidance tasks and spontaneous recovery of memory

Naive and pretrained rats were trained in two active avoidance paradigms using a pole-climbing box and in a single-trial passive avoidance task using a T-maze. They were then subjected to amnestic treatments with electroshock, leptazol, pentobarbitone, or ether anesthesia. Single retention tests were given at 20–24, 44–48, or 68–96 h postreatment. Electroshock and leptazol seizures produced retrograde amnesia in all three paradigms, provided that seizures were maximal and retention was tested before 48 h. Prior treatment with anticonvulsant drugs prevented amnesia. Ether and pentobarbitone anesthesia failed to produce amnesia in all three tasks. A trend of recovery from amnesia was observed in the electroshock and leptazol groups when tested for retention 48–96 h posttreatment. On the other hand, the nonamnesic control, pentobarbitone, and ether groups showed signs of forgetting at these longer intervals. Consolidation failure and/or retrieval block was surmised to be the cause of amnesia; recovery was the possible result of removing the block.     

Effects of GBEE on memory impairment induced by scopolamine in mice and activity of AChE in cerebral cortex

OBJECTIVE The fruit of Ginkgo biloba L.is also known as Ginkgo nuts. Ginkgo has the effect of warming the lung, boosting qi, downbear phlegm, dispersing toxin, kil ing worms and etc, which also recorded in ancient books on tumor treatment. The scientific name of succulent skin is exocarp in Gingko nuts. Research shows that GBEE(Ginkgo biloba exocarp extracts) has anti-tumor,anti-aging and immune promoting activity. As an M receptor blocker, scopolamine can block the excitatory effect of acetylcholine on M receptors, causing learning and memory dysfunction. It can partially simulate some features of the cholinergic system of Alzheimer disease(AD). The learning and memory impairment model of scopolamine is the classic screening model for AD drug research. In this paper, the effects of GBEE on scopolamine induced learning and memory impairment in mice and its mechanism were preliminarily studied. METHODS GBEE was prepared by the patented method(patent: ZL201610916394.4). Infrared Spectroscopy(IR) analysis shows that the proteoglycan in GBEE is ester linkage. The total content of proteoglycan in GBEE was 62.6%-64.8%, which was measured by phenol sulfuric acid method and brilliant blue method. Pre-column derivatization high-performance liquid chromatography(HPLC) detection showed that the proteoglycan in GBEE contains 6 kinds of monosaccharides including mannose, rhamnose, galacturonic acid, glucose, galactose, arabinose and 14 kinds of amino acids including aspartic acid, glutamic acid, glycine,serine, threonine, alanine, proline, valine, methionine,isoleucine, leucine, phenylalanine, tryptophan and lysine.60 ICR mice, half male and half female, 6-8 weeks old and weight(18-22) g, were randomly divided into six groups: blank control group(normal saline), model group(normal saline), positive drug group( donepezi 1.25 mg·kg-1)and GBEE low-does(50 mg·kg-1), medium-does(100 mg·kg-1) and high-does(200 mg·kg-1) groups. The drug were infused to stomach of mice once a day for 14 d,after that model of learning disorder and dysmnesia were made by intraperitoneal injection of scopolamine hydrobromide(3 mg·kg-1) in six groups except the blank control group on days 15-19. Morris water maze experiment was performed by using the mice′s instinct of escaping from the water to find rest platform. The mean escape latency(s), in other words, the time needed for searching platform was detected on days 15-18, the time in platform annulus(s) was detected on day 19. Each test was performed 30 min after intraperitoneal injection and 1 h after intragastric administration. The mean escape latency(s) and the time in platform annulus(s) were correlated with the memory ability of mice, the former was negatively correlated, the latter was positively correlated, so as to evaluate the changes of learning and memory ability of each group of mice. After the behavioral experiment, the brain tissues of mice were taken out immediately, and the cerebral cortex and hippocampus were cut and stored in the refrigerator at-80℃ with the help of the mouse brain mold. During the test, the brain homogenate was prepared by ultrasonic method, and the activity of acetylcholin esterase(AChE) in the cerebral cortex and hippocampus of each group of mice was measured according to the instructions of AChE test box. RESULTS Scopolamine can significantly prolong the mean escape latency(s) of Morris water maze experiment in mice, and shorten the time in platform annulus(s), which is statistically significant compared with the control group(P<0.05,P<0.01). The results showed that scopolamine caused the decrease of learning and memory ability in the model group. The time required to search for the platform in mice of positive drug group and the GBEE of the three dose groups was significantly reduced on the third and fourth days of Morris water maze experiment test. Except for the GBEE low-dose group, the comparison with the model group was statistically significant(P<0.05, P<0.01). On day 19, positive medicine and three dose groups GBEE can significantly extend the time in platform annulus(s), compared with model group(P<0.05,P<0.01), the effect of medium-dose GBEE group is better than that of high dose, close to the positive drug, the results showed that it could improve the learning and memory ability of scopolamine-induced memory impairment modle mice. While the memory ability of the scopolamine model group was decreased, AChE activity in the cerebral cortex of the mice was significantly increased compared with the control group(P<0.05). Donepezil and GBEE in each dose could reduce Ach E activity in the cerebral cortex of the mice. Except for the high-dose GBEE group, there were significant differences between the other groups and the model group(P<0.05). The results of AChE activity in hippocampi need to be repeated further because of the large difference. CONCLUSION GBEE can improve the learning and memory ability of scopolamine induced memory impairment model mice,and the mechanism may be related to reducing the activity of cerebral AChE and reducing the inactivation of cholinergic neurotransmitter ACh in memory impairment mice.AD is a kind of neural degenerative disease, which can easily be seen in the middle-aged and old people, the early disease mainly for hypomnesis, dysmnesia and so on, accompanied by the reduction of acetylcholine(ACh), the increasing of AChE activity. Early stage of AD is the best treatment stage, by improving the memory function, which can effectively prevent the further development of AD, slow disease progression and reduce disease severity. This study shows that GBEE has certain potential in the treatment of AD, which lays a foundation for further research on the effect and mechanism of GBEE on AD.     

Evidence for GABA-BZ receptor modulation in short-term memory passive avoidance task paradigm in mice

The possible involvement of gamma-aminobutyric acid/benzodiazepine (GABA-BZ) receptor modulation in scopolamine-induced short-term memory deficit was investigated in mice. Passive avoidance step-down task behavior was observed. Latency of mice to reach shock-free zone (SFZ) and number of mistakes the animal made in 15 min were used as separate parameters for acquisition and memory retention, respectively. Scopolamine (0.3 mg/kg) caused a delay in reaching SFZ and an increased number of mistakes. Physostigmine reversed the scopolamine-induced increase in number of mistakes; however, it caused a delay in the time to reach SFZ. Subeffective dose of GABA, when combined with physostigmine, further delayed the latency to reach SFZ, but reduced the number of mistakes very significantly. GABA (50, 75 and 100 mg/kg, i.p.) and GABA agonists sodium valproate (30 and 60 mg/kg, i.p.), fengabine (5 and 10 mg/kg, i.p.), (+/-)baclofen (0.25, 0.5 and 1.0 mg/kg, i.p.) and (-)baclofen (0.25 and 0.5 mg/kg i.p.) reversed the scopolamine-induced effect; however, sodium valproate at higher dose delayed time to reach SFZ. Combined administration of lower dose (+/-)baclofen and subeffective dose of GABA showed significant decrease in latency and number of mistakes in scopolamine-treated animals. The specific benzodiazepine antagonist flumazenil (Ro-15-1788) (5 and 10 mg/kg, i.p.) and inverse agonist FG-7142 (10 mg/kg, i.p.) very significantly reversed scopolamine-induced increase in number of mistakes, but Ro-15-1788 failed to show any effect on latency per se and in scopolamine-treated experiments, as well.(ABSTRACT TRUNCATED AT 250 WORDS)     

Opposite effects induced by low and high doses of apomorphine on single-trial passive avoidance learning in mice

The effects of apomorphine (0.0125-1 mg/kg, SC), a dopamine (DA) agonist, on passive avoidance learning were assessed in mice which received brief and long foot-shocks in a training test. At low doses, apomorphine stimulates DA autoreceptors. With a shock of brief duration, apomorphine at a low dose (0.05 mg/kg), enhanced the avoidance learning when it was administered 20 min before the training test or the retention test. At high doses, apomorphine stimulates postsynaptic DA receptors. With a shock of long duration, apomorphine at a high dose (1 mg/kg), impaired the avoidance learning when it was administered 20 min before the training test or the retention test. However, apomorphine (0.05 and 1 mg/kg) given immediately after the training test did not have any effect on the avoidance behavior with shocks of either brief or long durations. Apomorphine-induced enhancement of passive avoidance learning was antagonized by sulpiride, but not by haloperidol. These results show that apomorphine induced the opposite effects on the passive avoidance learning depending on the dose or on the reinforcement intensity and suggest that the central DA system may play an important role in modulating memory processes.