Retention Of Passive Avoidance Learning Research Articles

Intracerebroventricular microinjection of kaempferol on memory retention of passive avoidance learning in rats: involvement of cholinergic mechanism(s)

Purpose of the study: Kaempferol (KM) is a flavonoid found in plant-derived foods and medicinal plants. Recently, it is well established that KM plays a protective role to develop Alzheimer's disease. The current study aimed at evaluating the effect of intracerebroventricular micro-injection of KM on memory retention of passive avoidance learning (MRPAM) and identifying the potentially related cholinergic mechanisms (ChMs) in rats.Materials and methods: In the current study, male Wistar rats randomly divided into control, vehicle and KM (10, 20 and 40 μg/rat) groups. Moreover, MRPAM was evaluated by shuttle box test. The role of ChM was studied using non-selective and selective acetylcholine antagonists (scopolamine [SCN], 4-DAMP and methoctramine [MN], respectively) as well as pirenzepine (PZ) in combination with KM.Results: The employment of KM (40 μg/rat) improved the SCN-induced memory impairment in MRPAM. Co-treatment with KM (40 μg/rat) plus 4-DAMP significantly increased the step-through latency (STL, P < 0.05; 167 ± 28 s) and decreased the total dark chamber (TDC, P < 0.05; 121 ± 31 s) compared with those of the 4-DAMP group (STL: 75 ± 13 s; TDC: 178 ± 46 s). Co-treatment with KM (40 μg/rat) plus PZ attenuated STL, and also increased TDC (P < 0.01; 220 ± 28 s) compared with those of the PZ group. Co-treatment with KM (10 and 20 μg/rat) and MN increased STL (P < 0.05), and deceased TDC compared with those of the MN group (P < 0.01).Conclusions: Totally, the results of the present study showed that cholinergic system may be involved in improving effect of KM on SCN-induced memory impairment.

Interaction between the antioxidant activity of curcumin and cholinergic system on memory retention in adult male Wistar rats.

The cholinergic system plays an important role in learning and memory. This study investigated the effects of curcumin (turmeric extract) and the cholinergic system and their interaction on memory retention of passive avoidance learning in adult male Wistar rats. At first, an injection cannula was implanted in right ventricles of the animals. One week after the surgery, the animals were trained with a shuttle box set up. Post-training, injections were performed in all experiments. Administration of curcumin increased memory retention. Also administrations of nicotine and pilocarpine, the cholinergic receptor agonists, increased memory retention, while it is decreased by succinylcholine and scopolamine, the cholinergic receptor antagonists. Then co-administration of curcumin and cholinergic drugs were performed. Intraperitoneal and intracerebroventricular injections were applied for the curcumin and cholinergic drugs, respectively. Co-administration of curcumin (45 mg/kg) with a low dose of nicotine (0.1 µg/rat) or pilocarpine (0.5 µg/rat) increased memory retention significantly. Effects of succinylcholine (0.01, 0.1 and 0.5 µg/rat) or scopolamine (0.1, 1 and 5 µg/rat) were attenuated by curcumin markedly (45 mg/kg). The results suggest that curcumin has a close interaction with cholinergic system in memory retention process.

Omega-3 fatty acids prevent LPS-induced passive avoidance learning and memory and CaMKII-α gene expression impairments in hippocampus of rat

BackgroundNeuroinflammation is considered to be a major factor in several neurodegenerative diseases. Recently, the polyunsaturated fatty acid omega-3 has been shown to have anti-inflammatory effects and might play an effective role in improving memory impairment due to inflammation. In order to test this, we stimulated neuroinflammation in an animal model and induced memory dysfunction as measured by reduced retention of passive avoidance learning (PAL) and altered expression of CaMKII-α, a gene known to be crucial for memory formation. We then investigated whether treatment with dietary omega-3 prevents inflammation-induced memory dysfunction in this model. MethodsMale wistar rats (200–220g) were fed either a control diet or a diet containing omega-3 (400mg/kg, po) for 1 month prior. Rats then received injection of either saline or LPS (500μg/kg, ip) and were subjected to the PAL acquisition task. The retention test was performed 24h later, and animals were sacrificed immediately. Hippocampi were dissected and stored at −80°C. Finally, TNF-α levels and CaMKII-α gene expression were measured by ELISA and qRT-PCR, respectively. ResultsWe found that LPS treatment significantly impaired PAL and memory, increased TNF-α levels and impaired CaMKII-α gene expression. In control and LPS-injected animals, pre-treatment with omega-3 improved performance on the PAL task and increased CAMKII-α gene expression. ConclusionTaken together, these data suggest that dietary omega-3 may improve cognitive function and provide a potential therapy for memory impairment due to neuroinflammation.

N-methyl-D-aspartate Receptors Are Involved in Caffeine-Induced Facilitation on Memory Retention of Passive Avoidance Learning in Rats

Background: Caffeine is an antagonist of adenosine receptors. It preserves cognition and reduces neurodegeneration. The MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has also shown amnesic properties in animal models. The effect of caffeine on MK-801-induced amnesia has not been the subject of any recent study. Methods: In this study, the effects of different doses (10 and 30 mg/kg) of caffeine on Wistar male rats (eight in each group), passive-avoidance (PA) response, and the impairment of this response by the NMDA receptor antagonist MK-801 (dizocilpine) were evaluated. The PA response was examined by measuring the step-through latency, 1 and 3 days after the animals received foot-shock training. Results: When given intraperitoneally before the training session, 10 mg/kg caffeine elongated the PA response, but 30 mg/kg did not, and it even reduced the step-through latency significantly. Before and after training, administration of 0.2 mg/kg MK-801 significantly elongated the PA response. This finding showed that MK-801 had a detrimental effect on learning, consolidation, and memory. We found the first evidence that pre-training and pre-testing administration of 10 mg/kg caffeine significantly reversed the learning and memory consolidation process disrupted by MK-801. Conclusion: These results show an interaction between caffeine and the glutamatergic system, suggesting that low-dose caffeine can prevent learning deficit and amnesia produced by a NMDA antagonist in rats (model of schizophrenia in human) when injected in pre- and post-training phase and may be clinically useful for treating cognitive impairments in schizophrenia.

Age-related cognitive decline and nesting behavior in an APPswe/PS1 bigenic model of Alzheimer's disease

A large series of 3-, 6-, 9-, and 12-month-old bigenic mice (N=240) with Swedish APP and A246E PS1 mutations was investigated in nest-building, spontaneous alternation, and two learning tasks. Progressive cognitive impairment was observed in APPswe/PS1 mice relative to controls for nest-building, spontaneous alternation, the reversal phase of left–right discrimination learning in a water-filled T-maze, and in retention of passive avoidance learning. The behavioral deficits in transgenic mice start at 6 months, appearing to offer an opportunity for assessing potential therapeutic agents in attenuating or preventing Alzheimer's disease.

Cognitive and non‐cognitive behaviors in an APPswe/PS1 bigenic model of Alzheimer’s disease

Neuropsychiatric signs are critical in primary caregiving of Alzheimer patients and yet have been relatively ignored in murine models. In the present study, APPswe/PS1 bigenic mice had higher levels of irritability than non-transgenic controls as measured in the touch escape test. Moreover, APPswe/PS1 mice showed poorer nest building than controls and a higher duration of immobility in the forced swimming assay. These results are concordant with the hypothesis of increased apathy and depression-like behavior in an Alzheimer's disease model. In addition, APPswe/PS1 bigenic mice were deficient in retention of passive avoidance learning and left-right discrimination learning, concordant with previous findings in other Alzheimer-like models.

NMDA receptors are involved in Ginkgo extract-induced facilitation on memory retention of passive avoidance learning in rats

Herbal therapies are commonly used to enhance memory and learning. Ginkgo biloba has shown to be one of the most popular herbs that is used to treat amnesia and retard age related memory deficits. Although, there have been several reports on the memory enhancing effects of Ginkgo, involvement of glutamatergic system that plays pivotal role in learning and memory has not been precisely assessed so far. The current study intended to investigate the effect of Ginkgo intake on amnesia while NMDA (N-methyl D-aspartic acid) receptors blocked by the administration of MK-801. The study used passive avoidance (PA) task to investigate the effect of chronic administration of Ginkgo extract (40 and 90 mg/kg; oral) on the memory span in male Wistar rats, suffering from MK-801-induced forgetfulness (0.06 and 0.1 mg/kg; i.p.). The results indicate that Ginkgo was able to remove MK-801-induced forgetfulness, indicating that Ginkgo can affect memory retention but not effect on passive avoidance acquisition, using pathways other than glutamatergic system as well. The results might indicate that Ginkgo extract can be effective in removing forgetfulness caused by inhibiting NMDA receptors from performing their activities.

Effects of Salvia officinalis L. (sage) leaves on memory retention and its interaction with the cholinergic system in rats

Objective The leaves of sage ( Salvia officinalis L., Lamiaceae) are reported to have a wide range of biological activities, such as anti-bacterial, fungistatic, virustatic, astringent, eupeptic and anti-hydrotic effects. To determine the mnemogenic effect of sage leaves, we investigated the effects of ethanolic extract of sage leaves and its interaction with cholinergic system on memory retention of passive avoidance learning in rats. Methods Post-training intracerebroventricular (i.c.v) injections were carried out in all the experiments except ethanolic extract (i.p. intraperitoneally). Results Administration of ethanolic extract (50 mg/kg), pilocarpine (0.5 and 1 mg/rat), the muscarinic cholinoceptor agonist, and nicotine (0.1 and 1 μg/rat) increased, while mecamylamine (1, 5 μg/rat), the muscarinic cholinoceptor antagonist, and mecamylamine (0.01 and 0.1 μg/rat), the nicotine cholinoceptor antagonist decreased memory retention in rats. Activation of muscarinic cholinoceptors by pilocarpine potentiated the response of ethanolic extract. Also, pharmacological blockade of scopolamine attenuated potentiating effect of ethanolic extract. Activation of nicotinic cholinoceptor by nicotine potentiated the response of ethanolic extract. Blockade of nicotinic cholinoceptor by mecamylamine attenuated the response of ethanolic extract. Conclusion It is concluded that the ethanolic extract of salvia officinalis potentiated memory retention and also it has an interaction with muscarinic and nicotinic cholinergic systems that is involved in the memory retention process.

Effects of a Novel Cognitive Enhancer, Spiro[imidazo-[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446), on Learning Impairments Induced by Amyloid-β1–40 in the Rat

We have previously shown that intracerebroventricular (i.c.v.) infusion of amyloid-beta (Abeta)1-40 produces oxidative stress and cholinergic dysfunction, as well as learning and memory deficits, in rats. In the present study, effects of a newly synthesized azaindolizinone derivative, spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446), were assessed in rats with learning deficits induced by Abeta1-40 or scopolamine. The i.c.v. infusion of Abeta1-40 caused impairments in spontaneous alternation behavior in a Y-maze task, spatial reference and short-term memory in a water-maze task, and retention of passive-avoidance learning. Abeta1-40-infused rats also showed reduction in choline acetyltransferase (ChAT) activity in the medial septum and hippocampus, but not in the basal forebrain and cortex, and a decrease in glutathione S-transferase (GST)-like immunoreactivity in the cortex. Nicotine-stimulated acetylcholine (ACh) release in Abeta1-40-infused rats was lower than that in vehicle-infused rats. Oral administration of ZSET1446 at the dose range of 0.01 to 1 mg/kg ameliorated Abeta1-40-induced learning impairment in Y-maze, water-maze, and passive-avoidance tasks. ZSET1446 reversed the decrease of ChAT activity in the medial septum and hippocampus, GST-like immunoreactivity in the cortex, and nicotine-stimulated ACh release of Abeta1-40-treated rats to the levels of vehicle-infused control rats. Furthermore, 0.001 to 0.1 mg/kg ZSET1446 showed ameliorative effects on learning impairments caused by scopolamine in a passive-avoidance task. These results suggest that ZSET1446 may be a potential candidate for development as a therapeutic agent to manage cognitive impairment associated with conditions such as Alzheimer's disease.

NMDA receptor blockers prevents the facilitatory effects of post-training intra-dorsal hippocampal NMDA and physostigmine on memory retention of passive avoidance learning in rats

In the present study, the effects of post-training intra-dorsal hippocampal (intra-CA1) injection of an N-methyl- d-aspartate (NMDA) receptor agonist and competitive or noncompetitive antagonists, on memory retention of passive avoidance learning was measured in the presence and absence of physostigmine in rats. Intra-CA1 administration of lower doses of the NMDA receptor agonist NMDA (10 −5 and 10 −4 μg/rat) did not affect memory retention, although the higher doses of the drug (10 −3, 10 −2 and 10 −1 μg/rat) increased memory retention. The greatest response was obtained with 10 −1 μg/rat of the drug. The different doses of the competitive NMDA receptor antagonist DL-AP5 (1, 3.2 and 10 μg/rat) and noncompetitive NMDA receptor antagonist MK-801 (0.5, 1 and 2 μg/rat) decreased memory retention in rats dose dependently. Both competitive and noncompetitive NMDA receptor antagonists reduced the effect of NMDA (10 −2 μg/rat). In another series of experiments, intra-CA1 injection of physostigmine (2, 3 and 4 μg/rat) improved memory retention. Post-training co-administration of lower doses of NMDA (10 −5 and 10 −4 μg/rat) and physostigmine (1 μg/rat), doses which were ineffective when given alone, significantly improved the retention latency. The competitive and noncompetitive NMDA receptor antagonists, DL-AP5 and MK-801, decreased the effect of physostigmine (2 μg/rat). Atropine decreased memory retention by itself and potentiated the response to DL-AP5 and MK-801. In conclusion, it seems that both NMDA and cholinergic systems not only play a part in the modulation of memory in the dorsal hippocampus of rats but also have demonstrated a complex interaction as well.

NMDA receptor antagonists antagonize the facilitatory effects of post-training intra-basolateral amygdala NMDA and physostigmine on passive avoidance learning

In the present study, the effects of post-training intra-basolateral amygdala (BLA) injection of an N-methyl- d-aspartate (NMDA) receptor agonist and competitive or noncompetitive antagonists, on memory retention of passive avoidance learning was measured in the presence and absence of physostigmine in rats. Intra-BLA administration of lower doses of NMDA (10 − 5 and 10 − 4 μg/rat) did not affect memory retention, although higher doses of the drug (10 − 3 , 10 − 2 and 10 − 1 μg/rat) increased memory retention. The greatest response was obtained with 10 − 1 μg/rat of the drug. The different doses of the competitive NMDA receptor antagonist DL-AP5 (1, 3.2 and 10 μg/rat) and noncompetitive NMDA receptor antagonist MK-801 (0.5, 1 and 2 μg/rat) decreased memory retention in rats dose dependently. Both competitive and noncompetitive NMDA receptor antagonists reduced the effect of NMDA (10 − 2 μg/rat). In another series of experiments, intra-BLA injection of physostigmine (2, 3 and 4 μg/rat) improved memory retention. Post-training co-administration of lower doses of NMDA (10 − 5 and 10 − 4 μg/rat) and physostigmine (1 μg/rat), doses which were ineffective when given alone, significantly improved the retention latency. The competitive and noncompetitive NMDA receptor antagonists, DL-AP5 and MK-801, decreased the effect of physostigmine (2 μg/rat). Atropine decreased memory retention by itself and potentiated the response to DL-AP5 and MK-801. It may be concluded that amygdalar NMDA receptor mechanisms interact with cholinergic systems in the modulation of memory.

Effect of vitamin E on memory retention in rats: Possible involvement of cholinergic system

This study concerned effects of vitamin E and the cholinergic system on memory retention of passive avoidance learning in rats. Post-training intracerebroventricular (i.c.v.) injections were carried out in all experiments. Administrations of vitamin E (10, 25 and 50 μg/rat), nicotine (0.1 μg/rat) and pilocarpine (0.5 μg/rat), the muscarinic receptor agonist increased memory retention, while mecamylamine (0.01, 0.1 and 0.5 μg/rat), the nicotinic receptor antagonist and scopolamine (0.1, 1 and 5 μg/rat), the muscarinic receptor antagonist decreased memory retention. The combination of vitamin E with nicotine or pilocarpine showed potentiation. Effects of mecamylamine or scopolamine were attenuated by vitamin E. It is concluded that vitamin E has a close interaction with cholinergic system in memory retention process.

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.

Effects of histamine and cholinergic systems on memory retention of passive avoidance learning in rats

In the present study, the effects of the histamine and cholinergic systems on memory retention in adult male rats were investigated. Post-training intracerebroventricular injections were carried out in all the experiments. Cholinoceptor agonist, acetylcholine (1–10 μg/rat) or nicotine (1–10 μg/rat), increased, while a cholinoceptor antagonist, scopolamine (5–20 μg/rat), decreased memory retention. The response to acetylcholine was attenuated by scopolamine. Administration of histamine (5–20 μg/rat) reduced, but the histamine H 1 receptor antagonist, pyrilamine (10–50 μg/rat), and the histamine H 2 receptor antagonist, cimetidine (1–50 μg/rat), increased memory retention in rats. The histamine receptor antagonists attenuated the response to histamine. Histamine reduced the acetylcholine- or nicotine-induced enhancement. The histamine receptor antagonists enhanced the nicotine- or acetylcholine-induced response. Histamine potentiated the inhibitory effect induced by scopolamine. It is concluded that histaminergic and cholinergic systems have opposing effects on memory retention. Also, the histaminergic system elicits an interaction with the cholinergic system in memory retention.

Effects of α-adrenoceptor agonists and antagonists on histamine-induced impairment of memory retention of passive avoidance learning in rats

The effect of α-adrenoceptor agents on the impairment induced by histamine was measured for memory retention of passive avoidance learning in rats. Post-training intracerebroventricular (i.c.v.) injection was carried out in all the experiments. Histamine (5, 10 and 20 μg/rat) reduced, while a histamine H 1 receptor antagonist, chlorpheniramine (0.1, 1 and 10 μg/rat), increased memory retention. The histamine H 2 receptor antagonist, ranitidine (0.1, 1, 10 and 20 μg/rat), did not elicit any response in this respect. Different doses of chlorpheniramine but not ranitidine reversed the histamine-induced impairment of memory. Clonidine and prazosin decreased, but yohimbine and phenylephrine increased, memory retention. Yohimbine decreased the inhibitory response to histamine. Phenylephrine, clonidine and prazosin did not alter the histamine effect. It is concluded that a histamine-induced impairment of memory retention through histamine H 1 receptors and an α 2-adrenoceptor mechanism may be involved in the histamine response.

Effects of histamine and opioid systems on memory retention of passive avoidance learning in rats

The present study investigated the effect of interactions between histamine receptor agents and the opioid peptidergic system on memory retention of passive avoidance learning in rats. Post-training intracerebroventricular (i.c.v.) injections were carried out in all the experiments. Administration of histamine (20 μg/rat) reduced, but the histamine H 1 receptor antagonist, pyrilamine (20 and 50 μg/rat), and the histamine H 2 receptor antagonist, cimetidine (10 and 50 μg/rat), increased memory retention in rats. The histamine receptor antagonists decreased the response induced by histamine. Morphine (1–10 μg/rat) reduced, while pentazocine (5 and 10 μg/rat) or the opioid receptor antagonist, naloxone (5 and 15 μg/rat), increased memory retention. The combination of histamine with morphine showed potentiation. Effects of pyrilamine and cimetidine were attenuated by morphine. The responses to pentazocine and naloxone also were decreased by histamine. It is concluded that the histaminergic system has an interaction with opioidergic system that is involved in the memory retention process.

Effects of intrahippocampal injection of GABAergic drugs on memory retention of passive avoidance learning in rats.

The effect of post-training intrahippocampal injection of gamma-aminobutyric acid (GABA) receptor agonists and antagonists, immediately after a training session on memory retention of passive avoidance learning in rats, was measured in the presence and absence of physostigmine. Post-training treatments were carried out in all the experiments. The different doses of the GABAA receptor agonist muscimol (2, 4 and 6 microg/rat) decreased memory retention in rats dose-dependently. The higher response was obtained with 6 microg/rat of the drug. When the GABAA receptor antagonist bicuculline (0.5, 1, 2 and 4 microg/rat) was administered, only one dose of the drug (1 microg/rat) increased memory retention; however, the antagonist reduced the effect of muscimol. The GABAB receptor agonist, baclofen (0.25, 0.5, 1 and 2 microg/rat) also reduced memory retention in the animals. Intrahippocampal injection of lower doses of the GABAB receptor antagonist CGP35348 (P-[3-aminopropyl]-p-diethoxymethyl-phosphinic acid) (2.5, 5, 10 microg/rat) did not effect memory retention, although the higher doses of the drug (25 and 50 microg/rat) decreased memory retention. The doses of antagonist (2.5, 5 and 10 microg/rat), which did not elicit any response alone, reduced the effect of baclofen. The inhibitory response of CGP35348 was also decreased by bicuculline. In another series of experiments, physostigmine improved memory retention. The GABA receptor agonists, muscimol and baclofen, as well as the GABA receptor antagonists bicuculline and CGP35348, decreased the effect of physostigmine. Atropine decreased memory retention by itself and potentiated the response of muscimol and baclofen. It is concluded that GABAA and GABAB receptor activation may be involved in the impairment of memory retention.

Calcium Channel Antagonists Enhance Retention of Passive Avoidance and Maze Learning in Mice

Although a number of studies have shown that treatment with calcium channel antagonists (CCAs) can ameliorate impairments in learning and memory in aged animals, evidence for a general nootropic effect of CCAs in neurologically normal young adult animals is ambiguous. This study attempts to resolve some of this ambiguity by comparing the effects of several CCAs on retention of passive avoidance learning and acquisition and retention of appetitively motivated spatial discrimination learning in young adult mice. Animals were trained in a step through passive avoidance apparatus and, immediately after training, injected subcutaneously with different doses of nimodipine, nifedipine, amlodipine, flunarazine, diltiazem, or verapamil. Retention was tested 24 h after training. In the maze-learning task mice were treated with the same doses of the aforementioned CCAs immediately after a brief training session in a linear maze and retention was tested 24 h after training. The most effective dose of each agent in the maze-retention experiment was administered to additional groups of animals 1 h prior to training to determine the effects of CCAs on acquisition processes. The effects of central administration of CCAs were examined by intracerebroventricular injection of different doses of amlodipine immediately after passive avoidance training. Results showed (1) all peripherally administered drugs except verapamil facilitated retention of passive avoidance training in a dose-dependent manner, (2) all drugs dose dependently facilitated retention of linear maze learning, (3) all doses of the drugs (except verapamil) which facilitated maze retention also facilitated maze learning, and (4) central administration of the dihydropyridine amlodipine produced a dose-dependent facilitation of the retention of passive avoidance learning. These data indicate that drugs which block calcium channels can enhance retention of two different types of learning in mice.

The mitochondrial benzodiazepine receptor and avoidance learning in the day-old chick

The specific mitochondrial benzodiazepine receptor (MBR) agonist, FGIN 1–27, and antagonist, PK 11195, were used to investigate whether this receptor was involved in passive avoidance memory formation in the day-old chick. PK 11195 at a concentration of 1–10 μM was found to be amnesic when injected directly into the lobus parolfactorius (LPO) 5 h after training ( P<.01). Unilateral injections of PK 11195 further showed that memory was only disrupted with injections into the right hemisphere ( P<.01). Since the MBR is considered to be involved in the production of a neurosteroid that modulates GABAergic transmission, we injected bicuculline and muscimol, specific inhibitor and agonist, respectively, of the GABA A receptor, to see if either disrupted memory formation. The results of bilateral injections into the LPO at 5 h post-training indicated that enhanced GABAergic transmission was involved in memory formation since the inhibitor, bicuculline, caused amnesia ( P<.01) and unilateral injections also showed that this effect was confined to the right hemisphere ( P<.05). Since memory for passive avoidance learning is thought to involve both cytosolic and mitochondrial protein synthesis at this 5-h time point [Freeman FM, Young IG. Chloramphenicol-induced amnesia for passive avoidance training in the day-old chick. Neurobiol Learn Mem 1999;71:80–93.], we studied the effect of unilateral injections of chloramphenicol (CAP) and anisomycin (ANI) during this second wave of protein synthesis and found that CAP only disrupted memory when injected into the right LPO 5 h post-training ( P<.05). This lateralization to the right hemisphere was also seen when ANI was injected 4 h post-training ( P<.05) but at 5 h, only bilateral injections of ANI could disrupt memory ( P<.05). The results suggest a role for mitochondria and the GABAergic system in the retention of passive avoidance learning in the day-old chick.

Protective effects of idebenone and alpha-tocopherol on beta-amyloid-(1-42)-induced learning and memory deficits in rats: implication of oxidative stress in beta-amyloid-induced neurotoxicity in vivo.

Amyloid beta-peptide (A beta), the major constituent of the senile plaques in the brains of patients with Alzheimer's disease, is cytotoxic to neurons and has a central role in the pathogenesis of the disease. Previous studies have suggested that oxidative stress is involved in the mechanisms of A beta-induced neurotoxicity in vitro. In the present study, we examined whether oxidative stress contributes to learning and memory deficits caused by continuous intracerebroventricular infusion of A beta-(1-42). In the A beta-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze and spatial memory in a water maze task were significantly impaired, as compared with A beta-(40-1)-infused control rats. The retention of passive avoidance learning was also significantly impaired by treatment with A beta-(1-42). Potent antioxidants idebenone and alpha-tocopherol prevented the behavioural deficits in Y-maze and water maze, but not passive avoidance, tasks in A beta-(1-42)-infused rats when they were repeatedly administered by mouth once a day from 3 days before the start of A beta infusion to the end of behavioural experiments. Lipid peroxide levels in the hippocampus and cerebral cortex of A beta-(1-42)-infused rats did not differ from those in control animals, and neither idebenone nor alpha-tocopherol affected the lipid peroxide levels. These results suggest that treatment with antioxidants such as idebenone and alpha-tocopherol prevents learning and memory deficits caused by A beta.