Avoidance Learning In Rats Research Articles

Active avoidance learning in rats with different audiogenic epilepsy proneness

The success of the formation of the conditioned reflex reaction of two-way avoidance in the shuttle chamber in rats of 3 strains was evaluated. These were rats predisposed to audiogenic epilepsy – the Krushinsky-Molodkina strain rats (KM), "4" strain (selected from a population of F2 hybrids of the KM strain and sound-insensitive Wistars) and rats of "0" strain, selected for the absence of audiogenic epilepsy from the same population (i. e. these strains, diametrically different in audiogenic epilepsy proneness, possessing a similar genetic background). Experiments have shown significantly more successful assimilation of this skill in rats of the "0" strain.

Active Avoidance Learning in Rats with Different Audiogenic Epilepsy Proneness

Active Avoidance Learning in Rats with Different Audiogenic Epilepsy Proneness

Converging Evidence on D-Amino Acid Oxidase-Dependent Enhancement of Hippocampal Firing Activity and Passive Avoidance Learning in Rats.

BackgroundN-methyl-D-aspartate (NMDA) receptor activation requires the binding of a co-agonist on the glycine-binding site. D-serine is the main endogenous co-agonist of NMDA receptors, and its availability significantly depends on the activity of the metabolic enzyme D-amino acid oxidase (DAAO). Inhibition of DAAO increases the brain levels of D-serine and modulates a variety of physiological functions, including cognitive behavior.MethodsHere, we examined the effects of a novel 4-hydroxypyridazin-3(2H)-one derivative DAAO inhibitor, Compound 30 (CPD30), on passive avoidance learning and on neuronal firing activity in rats.ResultsD-serine administration was applied as reference, which increased cognitive performance and enhanced hippocampal firing activity and responsiveness to NMDA after both local and systemic application. Similarly to D-serine, CPD30 (0.1 mg/kg) effectively reversed MK-801–induced memory impairment in the passive avoidance test. Furthermore, local iontophoretic application of CPD30 in the vicinity of hippocampal pyramidal neurons significantly increased firing rate and enhanced their responses to locally applied NMDA. CPD30 also enhanced hippocampal firing activity after systemic administration. In 0.1- to 1.0-mg/kg doses, CPD30 increased spontaneous and NMDA-evoked firing activity of the neurons. Effects of CPD30 on NMDA responsiveness emerged faster (at 10 minutes post-injection) when a 1.0-mg/kg dose was applied compared with the onset of the effects of 0.1 mg/kg CPD30 (at 30 minutes post-injection).ConclusionsThe present results confirm that the inhibition of DAAO enzyme is an effective strategy for cognitive enhancement. Our findings further facilitate the understanding of the cellular mechanisms underlying the behavioral effects of DAAO inhibition in the mammalian brain.

Movento effects on learning and hippocampal brain-derived neurotrophic factor protein of adult male rats.

Spirotetramat is a toxic commercially known as Movento used to control pistachio psylla pests. In the present study, the effects of Movento on passive avoidance learning of rats and their ability to explore the novel object in the novel object recognition test were investigated. The changes in the concentration of hippocampal brain-derived neurotrophic factor (BDNF) proteins were evaluated, too. Male Wistar rats were gavaged at different dosages of the Movento (50, 100, 250, 500, 1000, 1250, and 1500 mg/kg) or saline for 7 days (administered every 2 days). We showed that Movento caused 50 and 100% mortality at the dose of 1250 and 1500 mg/kg, respectively. At the dose of 1000 mg/kg, Movento significantly decreased locomotor activity (P < 0.05). These rats also displayed a significant decrease in the number of training trials in the shuttle box and the ability to recognize a novel object compared with the control group (P < 0.01). The BDNF protein level of hippocampus also showed a significant decrease in the Movento (1000 mg/kg) compared with the control group (P < 0.01) while the number of pancellular necrosis pyramidal CA1 cells increased significantly in the Movento group (P < 0.001). We concluded that exposure to Movento can decline sensory, motor, and learning in rats.

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.

Paradoxical influence of combined effect of Semax and ammonium molybdate on learning and memory in rats

The combined effect of Semax with water solutions of plumbum diacetate (10–7 M) and ammonium molybdate (10–5 M) on the two-way active avoidance learning in rats in the shuttle chamber was studied. It was established that both salts of heavy metals oppress the learning and memory; plumbum diacetate caused larger oppression. Semax slowed down the development of the conditioned response but counteracted the negative influence on this process from the side of both metals. The effect of Semax on the development of the avoidance reaction in the presence of ammonium molybdate, which oppressed the avoidance by itself, paradoxically intensified. During the combined effect of the peptide and ammonium molybdate, the development of the conditioned reaction occurred much faster than against the background of Semax without the combination with molybdenum. In total, data obtained indicate a counteraction of Semax to neurotoxic effect of plumbum and molybdenum salts. Since oxidative stress is the main mechanism of neurotoxic effect of heavy metals, the indicated positive effect of Semax can, in our opinion, confirm the presence of antioxidant properties in the spectrum of the peptide pharmacological activity.

Effects of RFamide-related peptide-1 (RFRP-1) microinjections into the central nucleus of amygdala on passive avoidance learning in rats

The amygdaloid body (AMY) plays an important role in memory, learning and reward-related processes. RFRP-1 immunoreactive fibers and NPFF receptors were identified in the AMY, and previously we verified that RFRP-1 infused into the central nucleus of AMY (CeA) induced place preference. The aim of the present study was to examine the possible effects of RFRP-1 in the CeA on passive avoidance learning. Male Wistar rats were examined in two-compartment passive avoidance paradigm. Animals were shocked with 0.5mA current and subsequently were microinjected bilaterally with 50ng or 100ng RFRP-1 in volume of 0.4μl, or 20ng NPFF receptor antagonist RF9 (ANT) alone, or antagonist 15min before 50ng RFRP-1 treatments into the CeA. Fifty nanogram dose of RFRP-1 significantly increased the step-through latency time, the 100ng RFRP-1 and the ANT alone were ineffective. The effect of 50ng RFRP-1 was eliminated by the ANT pretreatment. Our results suggest that intraamygdaloid RFRP-1 enhances learning processes and memory in aversive situations and this effect can specifically be prevented by ANT pretreatment.

Influence of morphine on medial prefrontal cortex alpha2 adrenergic system in passive avoidance learning in rats

The prelimbic region of the medial prefrontal cortex (mPFC) is a brain area crucial for memory, attention, and decision making. It has been shown that α2-adreneoceptors (α2-ARs) play a powerful role in regulating memory and attention functions in this region. Since many studies have demonstrated the impairment effect of morphine on memory through mPFC, we aimed to investigate the possible interaction between α2-ARs of the mPFC and morphine induced amnesia in passive avoidance learning in rats. Animals were bilaterally implanted with chronic cannulas in the mPFC, trained in the step-through type passive avoidance task, and tested 24h after training; step-through latencies were measured. Our data indicate that post-training i.p. administration of morphine (2.5, 5 and 7.5mg/kg) dose-dependently reduced the step-through latency, showing an amnesic effect. Post-training intra-mPFC administration of yohimbine (an α2-adrenergic antagonist, 0.125, 0.25 and 0.5μg/rat) and clonidine (an α2-adrenergic agonist, 0.001, 0.01 and 0.2μg/rat), dose dependently impaired memory retrieval. Furthermore, post-training intra-mPFC microinjection of ineffective doses of yohimbine or clonidine significantly reversed the inhibitory effect of morphine on memory retrieval. Furthermore, SKF96365 (a presynaptic calcium channel blocker) reduced yohimbine and showed slight inhibition of clonidine effect.These results suggest that α2-ARs of the mPFC may play an important role in morphine-induced amnesia.

Effect of the hydroalcoholic extract of pistachio on avoidance learning in male Wistar rats

Received: December 2015, Accepted: January 2016 Background: Pistachio is a plant that has long been cultivated in different parts of Iran. Pistachios are very nutritious and contain vitamins E and B, flavonoids, antioxidants, and carotenoids. Since the pistachio is effective in the treatment of some neurological disorders and is indigenous to Iran and considering the substantial use of this nut, it is necessary to investigate its effects on cognitive functions of the brain. This study aimed to investigate the effect of the hydroalcoholic extract of the pistachio on avoidance learning in rats. Materials and Methods: In this experimental study, 40 male Wistar rats (200-250 g body weight and 2-3 months of age) were divided into 4 groups. Dimethyl sulfoxide (DMSO) 2.5% (vehicle) and hydroalcoholic extract of the pistachio (10, 50, and 100 mg/kg/day) were administered by gavage for 14 days. Avoidance learning test was performed using the shuttle box. Results: The results of this study indicated a significant increase in the latency to enter the dark room in the groups receiving different doses of pistachio extract compared to vehicle treated group. Moreover, in the treated groups, time spent in the dark room was decreased compared to the vehicle group. The comparison of different doses of pistachio extract demonstrated that 100 mg/kg was more effective than 10 and 50 mg/kg of the extract. Conclusions: The results of this study indicated that treatment of rats with pistachio extract, which is rich in vitamins, flavonoids, and antioxidant compounds, can improve learning and memory.

Effect of Amyloid β- Peptide on Passive Avoidance Learning in Rats: A Behavioral Study

Background: Alzheimer's disease (AD) is the most common form of dementia that leads to neurotoxicity. Amyloid β-peptide (Aβ) has a pivotal role in the pathogenesis of AD. Objectives: Given the contradictory results of Aβ (25-35) on the memory, in the present study we have examined the effect of Aβ induced memory impairment. Materials and Methods: Wistar male rats received an intrahippocampal (IHP) injection of Aβ (25-35).The learning function in the rats was examined by the passive avoidance task. Results: The results showed that Aβ (25-35) significantly impaired both step-through latency and time in dark compartment in the passive avoidance task. Conclusions: These data suggest that single bilateral microinjection of Aβ (25-35) could impair memory and can be used as an AD model in Wistar rats.

Erratum to: Involvement of Neurotransmitters in the Action of the Nociceptin/Orphanin FQ Peptide-Receptor System on Passive Avoidance Learning in Rats

Erratum to: Involvement of Neurotransmitters in the Action of the Nociceptin/Orphanin FQ Peptide-Receptor System on Passive Avoidance Learning in Rats

Involvement of neurotransmitters in the action of the nociceptin/orphanin FQ peptide-receptor system on passive avoidance learning in rats.

The nociceptin/orphanin FQ peptide (NOP) receptor and its endogenous ligand plays role in several physiologic functions of the central nervous system, including pain, locomotion, anxiety and depression, reward and drug addiction, learning and memory. Previous studies demonstrated that the NOP-receptor system induces impairment in memory and learning. However, we have little evidence about the underlying neuromodulation. The aim of the present study was to investigate the involvement of distinct neurotransmitters in the action of the selective NOP receptor agonist orphan G protein-coupled receptor (GPCR) SP9155 P550 on memory consolidation in a passive avoidance learning test in rats. Accordingly, rats were pretreated with a nonselective muscarinic acetylcholine receptor antagonist, atropine, a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, bicuculline, a D2, D3, D4 dopamine receptor antagonist, haloperidol, a nonselective opioid receptor antagonist, naloxone, a non-specific nitric oxide synthase inhibitor, nitro-L-arginine, a nonselective α-adrenergic receptor antagonist, phenoxybenzamine and a β-adrenergic receptor antagonist, propranolol. Atropine, bicuculline, naloxone and phenoxybenzamine reversed the orphan GPCR SP9155 P550-induced memory impairment, whereas propranolol, haloperidol and nitro-L-arginine were ineffective. Our results suggest that the NOP system-induced impairment of memory consolidation is mediated through muscarinic cholinergic, GABA-A-ergic, opioid and α-adrenergic receptors, whereas β-adrenergic, D2, D3, D4-dopaminergic and nitrergic mechanisms are not be implicated.

Transmitter mediation of the anxiolytic action of apelin-13 in male mice

The widespread distribution of apelin-13 and apelin receptors in the brain and periphery suggests an important function of this neuropeptide in regulatory processes in the organism. In previous work we found that apelin-13 facilitates the consolidation of passive avoidance learning in rats. In the present work we demonstrate that apelin-13 exerts anxiolytic action in an elevated plus maze in mice. In order to assess the possible involvement of transmitters in this action, the animals were pretreated with the following receptor blockers in doses which themselves did not influence the behavioral paradigm: atropine (a nonselective muscarinic acetylcholine receptor antagonist), haloperidol (a D2, D3, D4 dopamine receptor antagonist), phenoxybenzamine (a nonselective α1-adrenergic receptor antagonist), methysergide (a nonselective 5-HT2 serotonergic receptor antagonist), propranolol (a β-adrenergic receptor antagonist), naloxone (a nonselective opioid receptor antagonist) and bicuculline (a γ-aminobutyric acid subunit A receptor antagonist. Phenoxybenzamine, haloperidol, propranolol and methysergide prevented the action of apelin-13, whereas atropine, naloxone and bicuculline were ineffective. The data suggest that apelin-13 elicits its anxiolytic action via α-adrenergic, dopaminergic, β-adrenergic and 5-HT2 serotonergic mediation.

Transmitter-mediated action of neuromedin S on Passive avoidance learning in rats

Transmitter-mediated action of neuromedin S on Passive avoidance learning in rats

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.

Effects of different doses of doxepin on passive avoidance learning in rats

Background:Studies have shown that Doxepin has anti-inflammatory effects and reduces oxidative stress. Due to the fact that other tricyclic antidepressants have been shown to have neuroprotective effects, this study aimed to investigate the effects of different doses of doxepin on passive avoidance learning in rats.Materials and Methods:Old male Wistar rats were used in this study. Doxepin was administered intraperitoneally (1, 5 and 10 mg/kg) for 21 days. Passive avoidance learning test was used for evaluation of learning and memory. Rats received foot electrical shock on fifteen day, and step through latencies were evaluated one week after the electrical shock in retention phase.Results:Administration of Doxepin considerably increased the step through latencies in the rats that received the doses of 1 and 5 mg/kg (P < 0.05). However, in the dose of 10 mg/kg, there wasn’t any significant change comparing to control group.Conclusion:These results indicate that Doxepin has desirable effects on cognitive functions in low doses. Therefore, Doxepin can be considered as memory enhancers that understanding the underling mechanisms need further investigation.

Functional correlation between GABAergic and dopaminergic systems of dorsal hippocampus and ventral tegmental area in passive avoidance learning in rats

The aim of the present study was to investigate the existence of possible functional correlation between GABA-A and dopamine (DA) receptors of the dorsal hippocampus and the ventral tegmental area (VTA) in passive avoidance learning. Two guide cannulas were stereotaxically implanted in the CA1 region of the dorsal hippocampus and the VTA of male Wistar rats. In order to measure memory retrieval, the animals were trained in a step-through type passive avoidance task and tested 24 h after training. Post-training intra-CA1 administration of a GABA-A receptor agonist, muscimol (0.01-0.02 μg/rat) dose-dependently impaired memory retrieval. Post-training intra-VTA administration of SCH23390 (a dopamine D1 receptor antagonist; 0.1-0.8 μg/rat) or sulpiride (a D2 receptor antagonist; 0.5-1.5 μg/rat) decreased the inhibitory effect of muscimol (0.02 μg/rat, intra-CA1) on memory retrieval. Intra-VTA administration of the same doses of SCH23390, but not sulpiride, decreased the step-through latencies. On the other hand, post-training administration of muscimol (0.02 μg/rat) into the VTA inhibited memory retrieval. The administration of SCH23390 (0.01-0.2 μg/rat) or sulpiride (0.1-1 μg/rat) into the CA1 region, immediately after training, had no effect on memory retrieval. Furthermore, the amnesic effect of intra-VTA administration of muscimol was significantly decreased by intra-CA1 administration of sulpiride (0.5 and 1 μg/rat, intra-CA1), but not SCH23390. The practical conclusion is that the relationship between the hippocampus and the VTA may regulate memory formation in passive avoidance learning. Also, the correlation between the hippocampus and VTA by a dopaminergic system may be involved in mediating muscimol-induced amnesia.

The effects of raubasine and dihydroergocristine on an age-related deficit in passive avoidance learning in rats

The effects of raubasine and dihydroergocristine on an age-related deficit in passive avoidance learning in rats

Memory Retrieval and the Passage of Time: From Reconsolidation and Strengthening to Extinction

An established memory can be made transiently labile if retrieved or reactivated. Over time, it becomes again resistant to disruption and this process that renders the memory stable is termed reconsolidation. The reasons why a memory becomes labile after retrieval and reconsolidates still remains debated. Here, using inhibitory avoidance learning in rats, we provide evidence that retrievals of a young memory, which are accompanied by its reconsolidation, result in memory strengthening and contribute to its overall consolidation. This function associated to reconsolidation is temporally limited. With the passage of time, the stored memory undergoes important changes, as revealed by the behavioral outcomes of its retrieval. Over time, without explicit retrievals, memory first strengthens and becomes refractory to both retrieval-dependent interference and strengthening. At later times, the same retrievals that lead to reconsolidation of a young memory extinguish an older memory. We conclude that the storage of information is very dynamic and that its temporal evolution regulates behavioral outcomes. These results are important for potential clinical applications.

Effects of substance P microinjections into the globus pallidus and central nucleus of amygdala on passive avoidance learning in rats

Substance P (SP) has been implicated in learning and memory processes. This peptide facilitated learning when injected peripherally or directly into the ventral pallidum. SP has high affinity for neurokinin-1 (NK-1) receptors. WIN51,708 is a potent NK-1 receptor antagonist that can inhibit the physiological effects of SP. Immunohistochemical experiments showed that the globus pallidus (GP) and the amygdaloid (AMY) body are rich in SP immunoreactive elements. Pallidal lesions cause learning deficits in active and passive avoidance paradigms. Serious memory deficits develop after lesions of AMY and its role in conditioned fear has been suggested. The aim of our study was to examine whether the SP microinjected into the GP or central nucleus of AMY (ACE) can modify negative reinforcement. Male Wistar rats were conditioned in a passive avoidance situation. Animals were microinjected with 0.4 μl of 10 ng SP, 100 ng SP or vehicle solution into the GP or the ACE. Results showed that 10 ng SP significantly enhanced passive avoidance learning in both structures, while 100 ng SP was ineffective. Retention examined 1 week later was diminished in the GP and still significant in the ACE. The possible involvement o NK-1 receptors in the effects of SP microinjected into the ACE was also studied. Prior treatment with WIN51,708 could block the SP effects on passive avoidance paradigm. Our results are the first to demonstrate that SP plays important roles, though in different ways, in learning and memory processes related to the GP and AMY.