Decreased Memory Retention Research Articles

Iron administered in the neonatal period changed memory, brain monoamine levels, and BDNF mRNA expression in adult Sprague–Dawley rats

BackgroundIron is one of the key microelements in the mammalian body and is the most abundant metal in the brain. Iron, a very important chemical element in the body of mammals, is the most abundant metal in the brain. It participates in many chemical reactions taking place in the central nervous system acting as a cofactor in key enzymatic reactions involved in neurotransmitter synthesis and degradation, dendritic arborization, and myelination. Moreover, iron accumulation in the brain has been implicated in the pathogenesis of neurogenerative disorders.Material and methodsThe aim of our study was to assess the influence of iron administered orally (30 mg/kg) to rats in the neonatal period (p12-p14) by testing the performance of rats in the open field and social interaction tests, and by evaluating the recognition memory, monoamine levels in some brain structures, and BDNF mRNA expression. The behavioral and biochemical tests were performed in adult p88-p92 rats.ResultsIron administered to rats in the neonatal period induced long-term deficits in behavioral tests in adult rats. It reduced the exploratory activity in the open field test. In the social interaction test, it induced deficits in the parameters studied, and decreased memory retention. Moreover, iron changed the brain monoamine levels in some studied brain structures and decreased the expression of BDNF mRNA in the hippocampus.ConclusionsAll earlier and our present results indicated that iron administered to rats in the neonatal period induced an increase in oxidative stress which resulted in a change in the brain monoamine levels and decreased BDNF mRNA expression which may play a role in iron-induced memory impairment in adult rats.

Phloridzin attenuates lipopolysaccharide-induced cognitive impairment via antioxidant, anti-inflammatory and neuromodulatory activities

BackgroundLipopolysaccharide (LPS) is known to produce neuroinflammation and memory impairment. Although phloridzin (a phenolic phytoconstituent) shows antioxidant- and anti-inflammatory activities, its ameliorative potential in LPS-mediated neuroinflammation and memory dysfunction remains unexplored. ObjectivesTo investigate the protective effect of phloridzin against LPS-mediated memory impairment and neuroinflammation in mice. MethodsDifferent groups of mice were treated with LPS (250 μg/kg) via intraperitoneal (ip) route to induce cognitive impairments. The animals were administered with phloridzin (10–20 mg/kg, oral) or donepezil (1 mg/kg, intraperitoneal), and memory functions were evaluated by Morris water maze (MWM) and Y-maze. At the end of the behavioral experiments, the animals were sacrificed and different biochemical parameters like acetylcholinesterase (AChE), brain derived neurotropic factor (BDNF), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD) and glutathione (GSH) concentration in the hippocampus and the cerebral cortex were estimated. ResultsWhile LPS administered animals showed significantly decreased memory retention in both MWM and Y maze, a significant reversal in all the parameters were observed following treatment with phloridzin. LPS-treated animals showed significantly decreased level of antioxidants (SOD and GSH), neurotropic factor (BDNF) and cholinergic transmission (increased AChE) and increased levels of inflammatory/oxidative markers (TNF-α, IL-6 and MDA) in hippocampus and cortex. These changes were alleviated after the treatment with phloridzin. ConclusionsPhloridzin may have neuroprotective role against LPS-induced neuroinflammation and memory impairment by virtue of its antioxidant, anti-inflammatory, and enhanced cholinergic signalling activity in the hippocampus and cerebral cortex.

The effect of alpha-2 adrenergic receptors on memory retention deficit induced by rapid eye movement sleep deprivation.

Objective(s): Evidence shows that sleep deprivation (SD) disrupts the formation of hippocampus-related memories. Moreover, α2 adrenergic receptors that are wildly expressed in the CA1 hippocampal region have a significant role in modulating both sleep and memory formation. In the present research, we wanted to investigate the effect of stimulation and blockage of CA1 α2 adrenergic receptors by clonidine (an agonist of α2 adrenergic receptor) and yohimbine (an antagonist of α2 adrenergic receptor), respectively, on memory retention impairment induced by REM SD (RSD) in rats. Materials and Methods:Multiple platform apparatus were used to induce RSD, and the passive avoidance task was used to assess memory consolidation. Clonidine and yohimbine were injected intra-CA1. Results:The results showed that RSD (for 24 and 36, but not 12 hr) decreased memory retention, with no effect on locomotion. Post-training intra-CA1 infusion of a subthreshold dose of yohimbine (0.001 μg/rat) did not alter, while clonidine (0.1 μg/rat) restored memory retention impairment induced by RSD (24 and 36 hr). Also, none of the interventions did not influence locomotor activity. Conclusion:Our data strongly showed that CA1 α2 adrenergic receptors have a critical role in RSD-induced memory retention impairment.

Copper decreases associative learning and memory in Drosophila melanogaster

Copper is an essential element to all living organisms. Repeated use of metal-enriched chemicals, fertilizers, and organic substances may cause contamination at a large scale. Altered levels of Cu2+ may result in harmful effects and can be associated with memory and cognitive dysfunction. Studying simple, genetically tractable organisms such as Drosophila melanogaster, can reveal important data on the neural basis of conditioning. D. melanogaster is an important alternative experimental model to assess the toxic response to metals. In the present study, the effects of copper on flies’ development and in learning and memory retention in male and female adult flies were investigated. We paired an odorant to pain perception and observed the aversion behavior over time. Exposure of D. melanogaster eggs to Cu2+ increased mortality of larvae, pupae, and adults and decreased memory retention in adults. Moreover, male flies demonstrated to be more susceptible to Cu2+ toxicity than females. The results therefore, reinforce the importance of controlling the anthropogenic heavy-metals soil contamination given their hazardous effects to living organisms.

Pharmacological modulation of the behavioral effects of social defeat in memory and learning in male mice.

Previous studies have demonstrated that repeated social defeat (RSD) stress only induces cognitive deficits when experienced during adulthood. However, RSD increases cocaine-rewarding effects in adult and adolescent mice, inducing different expressions of proBDNF in the ventral tegmental area. The aim of the present study was to evaluate the effect of cocaine administration in socially defeated adult or adolescent mice on learning, memory, and anxiety. Additionally, the role of BDNF was also studied. Adolescent and young adult mice were exposed to four episodes of social defeat or exploration (control), being treated with a daily injection of four doses of saline or 1mg/kg of cocaine 3weeks after the last social defeat. Other groups were treated with the TrkB receptor antagonist ANA-12 during this 21-day period. After this treatment, their cognitive and anxiogenic profiles were evaluated, along with the expression of BDNF, pCREB, and pERK1/2 in the dentate gyrus (DG) and basolateral amygdala (BLA). Cocaine induced an increased expression of pCREB and BDNF in the DG and BLA only in defeated animals. Although RSD did not affect memory, the administration of cocaine induced memory impairments only in defeated animals. Defeated adult mice needed more time to complete the mazes, and this effect was counteracted by cocaine administration. RSD induced anxiogenic effects only when experienced during adulthood and cocaine induced a general anxiolytic effect. Blockade of Trkb decreased memory retention without affecting spatial learning and modified anxiety on non-stressed mice depending on their age. Our results demonstrate that the long-lasting effects of social defeat on anxiety and cognition are modulated by cocaine administration. Our results highlight that the BDNF signaling pathway could be a target to counteract the effects of cocaine on socially stressed subjects.

Effects of thioTEPA chemotherapy on cognition and motor coordination.

Cancer survivorship has increased greatly as therapies have become more advanced and effective. Thus, we must now focus on improving the quality of life of patients after treatment. After chemotherapy, many patients experience chemotherapy-induced cognitive decline, indicating a need to investigate pathologies associated with this condition. In this study, we addressed cognitive impairment after thioTEPA treatment by assessing behavior and assaying cytokine production and the structure of dendrites in the hippocampus. Male mice were given three intraperitoneal injections of thioTEPA. Five weeks later, the mice underwent behavior testing, and brains were collected for Golgi staining and cytokine analysis. Behavior tests included y-maze and Morris water maze and licking behavioral task. Cytokines measured include: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-10, IL-12p70, MCP-1, TNF-α, GMCSF, and RANTES. We observed decreased memory retention in behavioral tasks. Also, dendritic arborization and length were decreased after chemotherapy treatment. Finally, thioTEPA decreased cytokine production in animals treated with chemotherapy, compared to saline-treated controls. Here, we used a mouse model to correlate the decreases in dendritic complexity and inflammatory cytokine production with cognitive impairment after chemotherapy.

The dorsal hippocampal group III metabotropic glutamate receptors are involved in morphine effect on memory formation in male mice

This study investigated the role of dorsal hippocampal (CA1) group III metabotropic glutamate (mGlu) receptors in impairment of memory formation and state-dependent memory induced by morphine. For this purpose, the CA1 area was cannulated and one-trial passive avoidance task was selected to assess the memory function. Morphine was administrated subcutaneously (s.c.) and mGlu receptors agonist or antagonist were microinjected into CA1 regions. The obtained results indicated that pre-training administration of morphine (5 mg/kg; s.c.) decreased memory retention. Moreover, pre-test administration of morphine (5 mg/kg; s.c.) induced morphine state–dependent memory retention under pre-training morphine effect (5 mg/kg; s.c.). Although, intra-CA1 microinjection of lower doses of group III mGlu receptors agonist, L-AP4, (10 and 20 mmol/mouse) and antagonist, CPPG, (10 and 15 mmol/mouse) did not affect memory retention, but higher dose of the drugs (30 mmol/mouse) decreased memory retention. Pre-test microinjection of L-AP4 (10, 20 and 30 mmol/mouse; intra-CA1) had no effect on morphine-induced amnesia, but same doses of L-AP4 plus an effective dose of morphine (1 mg/kg; s.c.) reversed morphine-induced amnesia. Interestingly, amnesia induced by pre-training morphine (5 mg/kg; s.c.) was significantly reversed by pre-test administration of CPPG (30 mmol/mouse; intra-CA1). On the other hand, pre-test co-administration of CPPG (10 and 15 mmol/mouse; intra-CA1) and morphine (5 mg/kg; s.c.) following pre-training morphine (5 mg/kg; s.c.) decreased memory retention. Taken together, our results suggested that morphine effects on memory formation might be mediated via the activity of dorsal hippocampal metabotropic glutamate receptors.

Neuroprotective role of GABAB receptor modulation against streptozotocin-induced behavioral and biochemical abnormalities in rats

Stimulation as well as inhibition of GABAB (Gamma amino butyric acid) receptors has been reported to show beneficial effects in Alzheimer’s disease (AD). Experimental evidences suggest that the use of GABAergic agents could influence learning and memory. The present study was designed to investigate the possible role of GABAB receptors in streptozotocin (STZ)-induced behavioral and biochemical abnormalities in rats. Herein STZ was infused (3mg/kg) bilaterally on alternate days (day 1 and day 3) to produce experimental dementia in rats. STZ-infused rats were then treated with baclofen (GABABR agonist) 5 and 10mg/kg i.p. and CGP35348 (GABABR antagonist) 25 and 50mg/kg i.p. one week following STZ infusion for 15days. Cognitive functions were assessed by using Morris water maze (MWM) and object recognition task (ORT). Levels of malondialdehyde (MDA.), reduced glutathione (GSH), andacetylcholinesterase (AChE) were determined to evaluate oxidative stress and cholinergic function. STZ-infused rats showed decreased memory retention, elevated levels of MDA, increased AChE activity, reduced GSH levels. The combination of STZ with increasing doses of Baclofen further induced a higher decrease in memory retention and increase in oxidative stress. CGP35348 restored cognitive functions and AChE activity in STZ-infused rats. The cognitive enhancement following CGP35348 may be due to its ability to restore cholinergic, serotonergic and dopaminergic function, and its antioxidant activity. Therefore, it would be safe to conclude that the pharmacological blockade of GABAB receptors would be therapeutic in the management of cognitive disorders such as Alzheimer’s disease.

Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction

Chronic stress has a detrimental effect on neurological insults, psychiatric deficits, and cognitive impairment. In the current study, chronic stress was shown to impair learning and memory functions, in addition to reducing in hippocampal Adenosine monophosphate-activated protein kinase (AMPK) activity. Similar reductions were also observed for brain-derived neurotrophic factor (BDNF), synaptophysin, and post-synaptic density-95 (PSD-95) levels, all of which was counter-regulated by a regime of regular and prolonged exercise. A 21-day restraint stress regimen (6h/day) produced learning and memory deficits, including reduced alternation in the Y-maze and decreased memory retention in the water maze test. These effects were reversed post-administration by a 3-week regime of treadmill running (19m/min, 1h/day, 6days/week). In hippocampal primary culture, phosphorylated-AMPK (phospho-AMPK) and BDNF levels were enhanced in a dose-dependent manner by 5-amimoimidazole-4-carboxamide riboside (AICAR) treatment, and AICAR-treated increase was blocked by Compound C. A 7-day period of AICAR intraperitoneal injections enhanced alternation in the Y-maze test and reduced escape latency in water maze test, along with enhanced phospho-AMPK and BDNF levels in the hippocampus. The intraperitoneal injection of Compound C every 4days during exercise intervention diminished exercise-induced enhancement of memory improvement during the water maze test in chronically stressed mice. Also, chronic stress reduced hippocampal neurogenesis (lower Ki-67- and doublecortin-positive cells) and mRNA levels of BDNF, synaptophysin, and PSD-95. Our results suggest that regular and prolonged exercise can alleviate chronic stress-induced hippocampal-dependent memory deficits. Hippocampal AMPK-engaged BDNF induction is at least in part required for exercise-induced protection against chronic stress.

Effect of Cornus mas fruit flavonoids on memory retention, level of plasma glucose and lipids in an intracerebroventricular streptozotocin-induced experimental Alzheimer’s disease model in Wistar rats

Poor nutrition, poor mobility, obesity and ageing increase the possibility of neuronal disorder and Alzheimer’s disease. This study examined effect of Cornus mas flavonoids on memory retention and the level of plasma glucose and lipids in an intra-cerebroventricular streptozotocin-induced experimental Alzheimer’s disease model in Wistar rats. Intracerebroventricular administration of streptozotocine (3 mg kg–1) was performed and the animals memory were evaluated through passive avoidance tasks. Five groups (saline-saline control, streptozotocine-saline, and streptozotocine with different flavonoid doses [5, 10, 20 mg kg –1 ]) were examined. Animals received different doses of C. mas flavonoids or saline for three weeks starting one day before surgery. Rat weight was measured at the beginning of each week. Injection of streptozotocine significantly reduced memory retention, compared to the control group. Flavonoid treatment increased memory retention in a dose-dependent manner, and triglyceride and glucose concentration decreased memory retention. At the same time, high-density lipoprotein concentration increased without any effect on low-density lipoprotein concentration. The dose of 10 mg kg –1 decreased rat weight significantly. Our findings show that C. mas flavonoids can optimize cognitive deficits caused by injections of streptozotocine and also have a few positive effects on reducing the risk factors in the serum.

The effect of combined treatment with escitalopram and risperidone on the MK-801-induced changes in the object recognition test in mice.

Atypical antipsychotic drugs have some efficacy in alleviating the negative and some cognitive symptoms of schizophrenia but those effects are small and mechanisms of this action are still unknown. A few clinical reports have suggested that the antidepressant drugs, especially selective serotonin reuptake inhibitors (SSRI) are able to augment the activity of atypical antipsychotic drugs, thus effectively improving treatment of the negative and some cognitive symptoms of schizophrenia. In the present study, we evaluated the effect of escitalopram (SSRI) and risperidone (an atypical antipsychotic drug), given separately or jointly, on the effect of MK-801 (a NMDA receptor antagonist) given before to the first introductory session, in the object recognition memory test. The mice were tested for the ability to discriminate between an old, familiar and a novel object. Escitalopram and risperidone were given 30min before MK-801, and MK-801 was administered 30min before the first introductory session. Memory retention was evaluated 90min after the introductory session. The obtained results showed that MK-801 (0.2mg/kg) decreased memory retention when given before the introductory session. Risperidone at a higher dose (0.1mg/kg) reversed that effect. Co-treatment with an ineffective dose of risperidone (0.01mg/kg) and escitalopram (5 or 10mg/kg) abolished the deficit of object recognition memory induced by MK-801. The obtained results suggest that escitalopram may enhance the antipsychotic-like effect of risperidone in the animal tests used for evaluation of some cognitive symptoms of schizophrenia.

Introgression study reveals two quantitative trait loci involved in interspecific variation in memory retention among Nasonia wasp species.

Genes involved in the process of memory formation have been studied intensively in model organisms; however, little is known about the mechanisms that are responsible for natural variation in memory dynamics. There is substantial variation in memory retention among closely related species in the parasitic wasp genus Nasonia. After a single olfactory conditioning trial, N. vitripennis consolidates long-term memory that lasts at least 6 days. Memory of the closely related species N. giraulti is present at 24 h but is lost within 2 days after a single trial. The genetic basis of this interspecific difference in memory retention was studied in a backcrossing experiment in which the phenotype of N. giraulti was selected for in the background of N. vitripennis for up to five generations. A genotyping microarray revealed five regions that were retained in wasps with decreased memory retention. Independent introgressions of individual candidate regions were created using linked molecular markers and tested for memory retention. One region on chromosome 1 (spanning ∼5.8 cM) and another on chromosome 5 (spanning ∼25.6 cM) resulted in decreased memory after 72 h, without affecting 24-h-memory retention. This phenotype was observed in both heterozygous and homozygous individuals. Transcription factor CCAAT/enhancer-binding protein and a dopamine receptor, both with a known function in memory formation, are within these genomic regions and are candidates for the regulation of memory retention. Concluding, this study demonstrates a powerful approach to study variation in memory retention and provides a basis for future research on its genetic basis.

Influence of mild traumatic brain injury during pediatric stage on short-term memory and hippocampal apoptosis in adult rats.

Traumatic brain injury (TBI) is a leading cause of neurological deficit in the brain, which induces short- and long-term brain damage, cognitive impairment with/without structural alteration, motor deficits, emotional problems, and death both in children and adults. In the present study, we evaluated whether mild TBI in childhood causes persisting memory impairment until adulthood. Moreover, we investigated the influence of mild TBI on memory impairment in relation with hippocampal apoptosis. For this, step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemistry for caspase-3 were performed. Male Sprague-Dawley rats were used in the experiments. The animals were randomly divided into two groups: sham-operation group and TBI-induction group. The mild TBI model was created with an electromagnetic contusion device activated at a velocity of 3.0 m/sec. The results showed that mild TBI during the pediatric stage significantly decreased memory retention. The numbers of TUNEL-positive and caspase-3-positive cells were increased in the TBI-induction group compared to those in the sham-operation group. Defective memory retention and apoptosis sustained up to the adult stage. The present results shows that mild TBI induces long-lasting cognitive impairment from pediatric to adult stages in rats through the high level of apoptosis. The finding of this study suggests that children with mild TBI may need intensive treatments for the reduction of long-lasting cognitive impairment by secondary neuronal damage.

Effect of combined treatment with mirtazapine and risperidone on the MK-801-induced changes in the object recognition test in mice

BackgroundSeveral clinical reports have suggested that the mirtazapine-induced augmentation of risperidone activity may effectively improve treatment of the negative and certain cognitive symptoms of schizophrenia. MethodsThe aim of the present study was to evaluate the effect of mirtazapine and risperidone, given separately or jointly, on the impact of MK-801(an NMDA receptor antagonist), given prior to the first introductory session, on the object recognition memory in mice. To this end, we used the object recognition test in which animals were tested for the ability to discriminate between an old, familiar and a novel object. Mirtazapine (2.5 or 5mg/kg) and risperidone (0.01mg/kg) were given 30min before MK-801, and MK-801 (0.1 or 0.2mg/kg) was administered 30min before the first introductory session. Memory retention was evaluated 1.5h after the introductory session. ResultsThe obtained results showed that MK-801 (0.2mg/kg) decreased memory retention when given before the introductory session. Co-treatment with risperidone (0.01mg/kg) and mirtazapine (2.5 or 5mg/kg) abolished the effect of MK-801, whereas those drugs given separately did not change the action of MK-801. ConclusionsThe obtained results suggest that mirtazapine may enhance the antipsychotic-like effect of risperidone in the animal test modeling some cognitive symptoms of schizophrenia. Further studies are necessary to elucidate its mechanism of action.

Extra-Cellular Signal-Regulated Kinase (ERK) is Inactivated Associating Hippocampal ARC Protein Up-Regulation in Sevoflurane Induced Bidirectional Regulation of Memory

Low dose sevoflurane is demonstrated to have neuronal excitatory effects in the central nervous system. Activity-regulated cytoskeleton protein (Arc) can be rapidly expressed in the hippocampus for the modulation of synaptic plasticity. The extracellular signal-regulated kinase (ERK) pathway is also involved in learning and memory by mediating signals and modifications. This study aims at exploring the mechanism of sevoflurane on memory by connecting the ERK pathway, Arc and inhibitory avoidance (IA) behavioral training. SD rats were randomly assigned to three groups (sham, 0.11 and 0.3 % SEV). Anesthesia was given by target dose of sevoflurane for 45 min and IA (0.4 mA, 2 s) was conducted on every subject immediately after inhalation. The memory retention latency was observed 24 h after. Another serial of rats were sacrificed for Western-blot and polymerase chain reaction (PCR) examination of hippocampal tissue after first IA. 24 h IA performance was compared among groups. The 0.11 % SEV group displayed an elevation of memory retention, while the 0.3 % SEV group had decreased memory retention, both showed statistical differences from the sham (air) group. PCR analysis of Arc mRNA levels showed that subanesthetic doses of sevoflurane did not change Arc transcription levels between groups. However, 0.11 % sevoflurane significantly increased Arc protein in the hippocampus, while 0.3 % sevoflurane reversed this (*P < 0.05, compared with the sham group). There was no difference in total ERK between groups. Expression of phosphorylated ERK was significantly increased upon exposure to sevoflurane in a does dependent manner. ERK was down-regulated with hippocampal ARC expression in sevoflurane induced bidirectional regulation of memory, potentially at a translational level of modification.

Effects of increasing durations of immobilization stress on plasma corticosterone level, learning and memory and hippocampal BDNF gene expression in rats

Stress effects on learning and memory are widely recognized, but less agreement exists on whether they are positive or negative as well as on their neuronal and neuromolecular correlates. Stress involves expression of certain genes such as neurotrophin BDNF (brain derived neurotrophic factor), which is also involved in learning, but results are not consistent. Here effects of stress on memory and BDNF expression were studied using on adult male rats exposed to “immobilization stress” for various “short” durations, i.e., 1-h, 3-h, 5-h and “long-term” ones (2-h/day for 1 week). Learning and memory was measured using passive avoidance testing (STL = step-through-latency scores) as well as plasma corticosterone (CSt) levels and hippocampal BDNF gene expression. CSt increased in the 3-h and longer stressed groups but differences were significant in the 5-h and 1-week stressed subgroups. Three and 5-h of stress markedly and significantly (60–69%, p < 0.01) decreased memory retention in the stressed animals, while 1-h of stress had no effect; prolonged stress (2-h daily for 1-week) increased memory significantly (33%, p < 0.05). Hippocampal BDNF gene expression increased in the 1-h and 3-h stressed groups (44%, p < 0.05 and 71%, p < 0.01); but this parameter steadily declined in the 5-h stressed group (26%, p < 0.05) and weeklong stressed group (6%, not significant). Statistical analysis revealed an apparent but significant negative correlation between changes in memory and those of BDNF gene expression, indicating that BDNF may possibly play a compensatory role, reversing deleterious effects of stress on hippocampal memory functions.

Natural variation in Drosophila larval reward learning and memory due to a cGMP-dependent protein kinase

Animals must be able to find and evaluate food to ensure survival. The ability to associate a cue with the presence of food is advantageous because it allows an animal to quickly identify a situation associated with a good, bad, or even harmful food. Identifying genes underlying these natural learned responses is essential to understanding this ability. Here, we investigate whether natural variation in the foraging (for) gene in Drosophila melanogaster larvae is important in mediating associations between either an odor or a light stimulus and food reward. We found that for influences olfactory conditioning and that the mushroom bodies play a role in this for-mediated olfactory learning. Genotypes associated with high activity of the product of for, cGMP-dependent protein kinase (PKG), showed greater memory acquisition and retention compared with genotypes associated with low activity of PKG when trained with three conditioning trials. Interestingly, increasing the number of training trials resulted in decreased memory retention only in genotypes associated with high PKG activity. The difference in the dynamics of memory acquisition and retention between variants of for suggests that the ability to learn and retain an association may be linked to the foraging strategies of the two variants.

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.

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.