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The role of hippocampal nitric oxide in passive avoidance learning
Hooman Eshagh Harooni,Nasser Naghdi,Ali Haeri Rohani,Hoori Sepehri1
Physiology and Pharmacology , 2009,
Abstract: : Introduction: Nitric oxide (NO) is a retrograde messenger in hippocampal synaptic plasticity which involves in learning and memory processes. Previous studies revealed that hippocampal pyramidal cells contain NO synthase (NOS) enzyme which produce NO and could be a promising target to evaluate the role of NO in brain cognitive functions. So in this study, using NOS inhibitor (L-NAME), we conducted an experiment to assess the role of NO in passive avoidance learning. Methods: For this purpose, adult male Wistar rats (200-250 gr) were bilaterally implanted into the CA1 region of hippocampus. A week after surgery animals subjected to behavioral tests. 25 min. before training, rats received different doses of L-NAME (5, 10 and 15 μg/0.5μl/side) into the CA1 of hippocampus. Retrieval tests were performed in three different stages after training as working or immediate memory (immediately after training), short-term memory (90 min. after training) and long-term memory (24 h after training). Results: Our finding showed that pre-training injection of 15 μg/0.5μl/side L-NAME significantly increased the number of step-through into dark chamber and decreased step-through latency, for immediate and short-term memory, respectively. Conclusion: These results suggested that hippocampal NOS inhibition impairs both immediate and short-term memory, but have no any significant effect on long-term memory. Thereby hippocampal NO may affect early on learning and memory in passive avoidance task.
Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats
Roesler, R.;Kuyven, C.R.;Kruel, A.V.S.;Quevedo, J.;Ferreira, M.B.C.;
Brazilian Journal of Medical and Biological Research , 1998, DOI: 10.1590/S0100-879X1998001200014
Abstract: the purpose of this research was to evaluate the role of hippocampal n-methyl-d-aspartate (nmda) receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. adult male wistar rats were surgically implanted with cannulae aimed at the ca1 area of the dorsal hippocampus. after recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-ma footshock, 24-h training-test interval). immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-μl infusion containing 5.0 μg of the nmda competitive receptor antagonist aminophosphonopentanoic acid (ap5) or vehicle (phosphate-buffered saline, ph 7.4). infusion duration was 2 min per side. pre-training infusion of ap5 impaired retention test performance (mean ± sem number of conditioned responses (crs) during retention test session was 16.47 ± 1.78 in the vehicle group and 9.93 ± 1.59 in the ap5 group; p<0.05). post-training infusion of ap5 did not affect retention (mean ± sem number of conditioned responses during retention test session was 18.46 ± 1.94 in the vehicle group and 20.42 ± 2.38 in the ap5 group; p>0.10). this impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since ap5 affected neither training session performance measured by the number of crs nor the number of intertrial crossings during the training session. these data suggest that nmda receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of nmda receptors in fear memory.
Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats  [cached]
Roesler R.,Kuyven C.R.,Kruel A.V.S.,Quevedo J.
Brazilian Journal of Medical and Biological Research , 1998,
Abstract: The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA) receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval). Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-μl infusion containing 5.0 μg of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5) or vehicle (phosphate-buffered saline, pH 7.4). Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean ± SEM number of conditioned responses (CRs) during retention test session was 16.47 ± 1.78 in the vehicle group and 9.93 ± 1.59 in the AP5 group; P<0.05). Post-training infusion of AP5 did not affect retention (mean ± SEM number of conditioned responses during retention test session was 18.46 ± 1.94 in the vehicle group and 20.42 ± 2.38 in the AP5 group; P>0.10). This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory.
Effect of Intrahippocampal Ghrelin Agonist Administration on Passive Avoidance Learning and Anxiety in Rats  [PDF]
F. Kajbaf,R. Ahmadi,R. Fatemi Tabatabaie,E. Safarpoor
Pakistan Journal of Biological Sciences , 2012,
Abstract: Hippocampus, Amygdale and dorsal raphe nucleus are the cerebral main structures involved in learning, memory and anxiety. Ghrelin increases the level of several hormones in these structures and affects learning, memory and anxiety-like behaviors. This study was performed to investigate the effect of ghrelin agonist on passive avoidance learning and anxiety in adult female rats in the presence and absence of ovary hormones. Five groups of rats, including control group with no injections, ovariectomized groups; one group receiving normal saline and other group receiving ghrelin agonist solution, surgery shocked (sham operated) groups; one group receiving saline and other group ghrelin agonist solution, were tested. Inside stereotaxis apparatus, two sided CA1 cannulae were used and 1 μL of saline or ghrelin agonist solution, at 3 nmol μL-1 concentration, was injected into each cannula. Passive avoidance learning was measured by using shuttle box and anxiety by elevated plus- maze. Ghrelin agonist increased the level of learning in surgery shocked group in comparison with control group. Anxiety-like behavior was seen in both ovariectomized and surgery shocked groups. Ghrelin agonist binds its own receptors in the hippocampus, thereby increases learning capability and induces anxiety-like behaviors. Proper management of these behaviors might be useful in controlling some forms of nervous system diseases in humans.
Influence of intracerebral administration of L-NAME in dorsal hippocampus (CA1) on WIN55, 212-2 induced state-dependent memory in the step-down passive avoidance test
Mohammad Nasehi,Morteza Piri,Mohammad Reza Zarrindast
Journal of Mazandaran University of Medical Sciences , 2009,
Abstract: (Received 28 February, 2009 ; Accepted 8 July, 2009)AbstractBackground and purpose: This study presents the effects of nitricoxide synthase inhibitor (L-NAME) on WIN55, 212-2 induced state-dependent memory of passive avoidance task, which were examined in mice. Materials and methods: Mice were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Also, two stainless-steel annuals were placed 1 min above CA1. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice.Results: Post-training intra-CA1 administration of WIN55, 212-2 (0.5 and 1 μg/mouse), dose-dependent decreased the memory retrieval. The memory impairment induced by post-training administration of WIN55, 212-2 (1μg/mouse), was restored by pre-test administration with the same dose of drug (1μg/mouse, intra-CA1). Single intra-CA1 administration of L-NAME (0.3, 1 and 3 μg/mouse), 5 minute pre-test could not alter memory retrieval. Also, in animals in which retrieval was impaired due to post-training administration of WIN55, 212-2 (1μg/mouse), pre-test intra-CA1 administration of L-NAME (0.3, 1 and 3 μg/mouse) 24 hours after training, could not restore memory retrieval. Furthermore, in animals which received both post-training (1μg/mouse) and pre-test injection of WIN55, 212-2 (1μg/mouse), the injection of L-NAME (3 μg/mouse, intra-CA1), 2 minute before pre-test administration decreased retrieval.Conclusion: These findings may demonstrate the involvement of NO in state-dependent memory induced by intra-CA1 administration of WIN55, 212-2.J Mazand Univ Med Sci 2009; 19(71): 1-9 (Persian)
The Role of CA1 Hippocampus NMDA Receptors to Passive Avoidance Task in Presence and Absence of ZnCl2 in Adult Male Rats
A.A . Moazedi,Z. Valizadeh,G. H.A. Parham
Journal of Biological Sciences , 2008,
Abstract: The present investigation on the modulatory effects of zinc on NMDA receptors in this study the effects of intra dorsal (CA1) hippocampus injection of NMDA receptor agonist and antagonist to passive avoidance task in the presence and absence of ZnCl2 have been investigated in adult male rats, by using step down apparatus. So, 10 groups (n = 8) rats were considered, first group as a control, the second group received 0.1 μg rat-1 NMDA in 0.5 μL saline for 4 days immediately after shock. Third group receives 1 μg rat-1 MK-801 in 0.5 μL saline 10 min before training for 4 days. Sham groups receive saline at the same condition. Five remain groups received 100 mg/kg/day ZnCl2 in drinking water for 2 weeks. Sixth group only receives 100 mg/kg/day ZnCl2, but other groups (7, 8, 9 and 10), in addition of consumption ZnCl2, receive drug or saline in the same condition to 2, 3, 4, 5 groups. While administration of NMDA improve the impairment effects on ZnCl2 consumption (p<0.05), present results showed that consumption of 100 mg/kg/day ZnCl2 on adult male rat`s impair both learning and memory (p<0.05) but administration of MK-801 increasing the impairment effects of ZnCl2 (p<0.05). It seems that consumption of zinc chloride influence on passive avoidance learning and memory by its effects on NMDA receptor subunits in the hippocampus.
Effect of Donepezil on Group II mGlu Receptor Agonist- or Antagonist-Induced Amnesia on Passive Avoidance in Mice  [PDF]
Tomoaki Sato,Koh-ichi Tanaka,Yoshiko Ohnishi,Masahiro Irifune,Takashige Nishikawa
Neural Plasticity , 2003, DOI: 10.1155/np.2003.319
Abstract: We examined the effect of the acetylcholinesterase (ACHE) inhibitor, donepezil hydrocloride (DONP), on group II metabotropic glutamate (mGlu) receptor agonist- or antagonist-induced amnesia in the step-through passive avoidance task in male mice. DCG-IV, a group II mGlu receptor agonist, at dose of 50 ng and LY341495, a group II mGlu receptor antagonist, at dose of 300 ng, significantly attenuated the latency on the step-through task. The subcutaneous injection of DONP at dose of 1 mg/kg 1 hour before passive avoidance performance ameliorated the amnesia induced by DCG-IV and LY341495, whereas donepezil alone did not affect task latency. The results suggest that activation of group II mGlu receptors and disinhibition of the cAMP/PKA signaling pathway (caused by group II mGlu receptor antagonist) have a negative action on step-through passive avoidance memory performance, and that group II mGlu receptors and ACh interact to modulate learning and memory function.
Can ovariectomy and learning affect prefrontal cortex GABAAα1 receptor distribution in passive avoidance model in rats?
Asiyeh Shojaee,Mahnaz Taherianfard,Maryam sharifi Sharifi
Physiology and Pharmacology , 2012,
Abstract: Introduction: The interaction between steroid hormones and neurotransmitters such as GABA has been proved. The regulation of muscimol binding to high-affinity GABAA receptors by estradiol and progesterone has been studied within distinct brain regions using in vitro quantitative autoradiography. There are few studies about the mechanism of the effect of steroid hormones on behaviors such as learning and memory and also distribution of GABAAα1 receptor in prefrontal cortex. Therefore, the aim of this study was to evaluate the effect of ovariectomy and passive avoidance learning on distribution of GABAAα1 receptor in prefrontal cortex of rat. Methods: Twenty Sprague-Dawley adult rats were randomly divided into four equal groups: intact without learning; intact with learning; ovariectomy without learning and ovariectomy with learning. The shuttle box was used for induction of passive avoidance learning. Immunohistochemical procedure was used for determination of GABAAα1 receptor distribution. Image Analyzer software was used for determination of color intensity. Results: The data showed that ovariectomy lead to a significant (p<0.05) reduction in GABAAα1 receptor distribution in cg1 (cingulate cortex area1), M1 (primary motor cortex) and M2 (secondary motor cortex). While learning in the presence of ovarian hormones induced a significant decrease (p<0.05) in GABAAα1 receptor distribution in Cg1, M1 and M2 of prefrontal cortex of rats, it significantly increased (p<0.05) receptor distribution in the same regions in the absence of ovarian hormones. Conclusion: According to these results ovariectomy and passive avoidance learning change the distribution of GABAAα1 receptor in Cg1, M1 and M2 regions of prefrontal cortex of rat.
Effect of butylated hydroxytoluene on passive avoidance learning in male rats
Mahnaz Taherianfard,Javad Sajedianfard,Bita Geramizadeh,Neda Jafari
Physiology and Pharmacology , 2012,
Abstract: Introduction: Butylated hydroxytoluene (BHT; 2, 6-di-tert-butyl-p-cresol) is one of the extensively used antioxidants in the food industry. It is used in low-fat foods, fish products, packaging materials, paraffin, and mineral oils. BHT is also widely used in combination with other antioxidants such as BHA, propyl gallate, and citric acid for the stabilization of oils and high-fat foods. On the other hand, some investigators have reported that BHT has psychotic effects. Therefore, the aim of the present study was to investigate the effect of BHT on learning and memory in a model of passive avoidance learning in male rats. Methods: Twenty-eight male rats weighting 180-260 g were used. Animals were divided into 4 groups: 1- control group (received sesame oil with the same volume as experimental groups); -2 experimental 1 (received BHT 25 mg/kg/day); 3- experimental 2 (received BHT 100 mg/kg/day) 4- experimental 3 (received BHT 150 mg/kg/day). BHT was administered by oral intake for 15 days. Learning and memory were assessed by a passive avoidance shuttle-box. Data were analyzed by one way ANOVA and Tucky's post-hoc test. The level of significant was set at P<0.05. Results: Our data showed that BHT at the doses of 25, 100 and 150 mg/kg/day significantly decreased the time spent in light compared to the control group. Conclusion: According to our results, BHT impairs learning and memory in passive avoidance learning.
Different Susceptibility to Neurodegeneration of Dorsal and Ventral Hippocampal Dentate Gyrus: A Study with Transgenic Mice Overexpressing GSK3β  [PDF]
Almudena Fuster-Matanzo, María Llorens-Martín, Elena Gómez de Barreda, Jesús ávila, Félix Hernández
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027262
Abstract: Dorsal hippocampal regions are involved in memory and learning processes, while ventral areas are related to emotional and anxiety processes. Hippocampal dependent memory and behaviour alterations do not always come out in neurodegenerative diseases at the same time. In this study we have tested the hypothesis that dorsal and ventral dentate gyrus (DG) regions respond in a different manner to increased glycogen synthase kinase-3β (GSK3β) levels in GSK3β transgenic mice, a genetic model of neurodegeneration. Reactive astrocytosis indicate tissue stress in dorsal DG, while ventral area does not show that marker. These changes occurred with a significant reduction of total cell number and with a significantly higher level of cell death in dorsal area than in ventral one as measured by fractin-positive cells. Biochemistry analysis showed higher levels of phosphorylated GSK3β in those residues that inactivate the enzyme in hippocampal ventral areas compared with dorsal area suggesting that the observed susceptibility is in part due to different GSK3 regulation. Previous studies carried out with this animal model had demonstrated impairment in Morris Water Maze and Object recognition tests point out to dorsal hippocampal atrophy. Here, we show that two tests used to evaluate emotional status, the light–dark box and the novelty suppressed feeding test, suggest that GSK3β mice do not show any anxiety-related disorder. Thus, our results demonstrate that in vivo overexpression of GSK3β results in dorsal but not ventral hippocampal DG neurodegeneration and suggest that both areas do not behave in a similar manner in neurodegenerative processes.
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