The effect of curcumin pre-treatment on morphine-induced inhibitory memory impairment and nitric oxide level in rat

Background: Curcumin, as a polyphenolic compound in turmeric plant, has a neuroprotective effect in the improvement of learning and memory. Curcumin has interaction with diverse molecules, e.g., nitric oxide (NO). The present study dealt with the effect of curcumin pre-treatment on morphine-induced inhibitory memory impairment and nitric oxide metabolites (NOx) level in rat. Materials and Methods: In this experimental study, rats (n=40) were divided into four groups (each group, 10 rats) and their memory was evaluated in an inhibitory memory apparatus: Control (saline gavage for 35 days+post-training saline (i.p.)); Curcumin (curcumin gavage (10 mg/kg for 35 days)+post-training saline (i.p.); Morphine (saline gavage for 35 days+post-training morphine (7.5 mg/kg/i.p.)); Curcumin+Morphine (curcumin gavage (35 days)+post-training morphine (i.p.)). In all groups, the memory of animals in the second day (test) was reported as the time delay (Sec.) to enter the dark chamber. The locomotor activity was evaluated using the open field. After behavioral tests, the brain of animals was removed under deep anesthesia for evaluating the NOx level using the Griess method. Results: The time delay to enter the dark chamber in Morphine and Morphine+Curcumin groups were decreased (P<0.001) and increased (P<0.01), compared to Control and Morphine groups, respectively. Tissue NOx levels in Morphine and Morphine+Curcumin groups were decreased (P<0.05) and increased (P<0.001), compared to Control and Morphine groups, respectively. Locomotor activity in open field did not show a significant difference in four groups (P>0.05). Conclusion: Curcumin improves the morphine-induced inhibitory memory impairment in rat, probably via the NO signaling pathway

Pentylenetetrazol and Morphine Interaction in a State-dependent Memory Model: Role of CREB Signaling

Introduction: State-dependent (STD) memory is a process, in which the learned information can be optimally retrieved only when the subject is in the state similar to the encoding phase. This phenomenon has been widely studied with morphine. Several studies have reported that Pentylenetetrazole (PTZ) impairs memory in experimental animal models. Due to certain mechanistic interactions between morphine and PTZ, it is hypothesized that PTZ may interfere with the morphine-STD. The cyclic adenosine monophosphate Response Element-Binding (CREB) is considered as the main downstream marker for long-term memory. This study was designed to determine the possible interaction between PTZ and morphine STD and the presumable changes in CREB mRNA. Methods: In an Inhibitory Avoidance (IA) model, posttraining morphine (2.5, 5, and 7.5 mg/kg-i.p.) was used. The pre-test morphine was evaluated for morphine-induced STD memory. Moreover, the effect of a pre-test PTZ (60 mg/kg-i.p.) was studied along with morphine STD. Locomotion testing was carried out using open-field. Eventually, using real-time-PCR, the CREB mRNA changes in the hippocampus were evaluated. Results: Posttraining MOR (7.5 mg/kg-i.p.) impaired IA memory (P<0.001). The pre-test injection of similar doses of morphine recovered the morphine-induced memory impairment (P<0.001). The pre-test PTZ impaired the IA memory recall (P<0.001); however, the pre-test PTZ along with morphine STD potentiated the morphine-induced STD (P<0.001). Alterations in CREB mRNA were observed in all groups. No difference was seen in the locomotor activity. Conclusion: Presumably, the certain interactive effect of PTZ on morphine-induced STD is mediated through gamma-aminobutyric acid and opioid systems via CREB signaling

Effect of Pentylenetetrazol on Morphine State-Dependent Memory in Rat

Abstract Background: Learning and memory are among the higher functions of the brain. State-dependent memory (STM) is a type of memory in which the recall of a learned behavior is happend only in the same sensory and physiologic condition in which the behavior is encoded. The STM is seen with some drugs, e.g. the morphine. The pentylenetetrazol (PTZ) is a durg which is used for the induction of seizure in experimental models. Some studies have been revealed different effects of the PTZ on brain higher function (learning, memory …). The aim of present study was to explore the effect of PTZ on morphine-induced STM. Materials and Methods: In this study, male adult Wistar rats (190-220 g) were used. Animals in 3 groups (n=8) during 3 sessions (learning/memory, STM and interaction) were studied. During 48 hour (training and test) the learning and memory of animals were studied in inhibitory avoidance apparatus. The step-through latency in the test day was used as a criterion for memory. Post-training injection of saline or morphine (2.5, 5 and 7.5 mg/kg-ip) in different groups was carried out. In addition, the pre-test injection of morphine at the same doses was made to study the STM. Moreover, the interaction of pre-test single-dose PTZ (60 mg/kg-ip) on STM was studied. The locomotion of the animals was measured using the open field. Results: The post-training injection of morphine (2.5, 5 and 7.5 mg/kg-ip) impaired the inhibitory memory of rats compared to control group (p<0.001). The post-training and pre-test injections of the same dose of morphine (7.5 mg/kg-ip) reversed the impaired memory compared to morphine (2.5 and 5 mg/kg-ip), (p<0.001). The pre-test PTZ (60 mg/kg-ip) maintained the morphine (7.5 mg/kg-ip) STM (p<0.001). Conclusion: The present study revealed that the post-training ip injection of different doses of morphine results in the impairment of inhibitory avoidance memory in rat. In addition, the pre-test injection of the same doses of morphine reverses the impaired memory. This process is called STM. Consequently, the pre-test injection of PTZ maintains the morphine STM

The effect of pre- and post-natal nitrate exposure on inhibitory avoidance memory in mice

Background: Nitric oxide (NO) is directly involved in mechanisms responsible for fetal neurogenesis and development. It has also been shown that NO can impair or improve learning and memory in different models. There is evidence that administration of nitrate can produce NO. This study aimed at examining the effect of pre- and post-natal nitrate exposure on inhibitory avoidance memory in mice and measuring the NO metabolites herein. Materials and Methods: In this experimental study, 28 pregnant mice were divided into 4 groups: 1) Control group (whose mothers received only drinking water during the pregnancy and post-natal), 2) Treatment Group (whose mothers received sodium nitrate (100 mg / l) in drinking water during the pregnancy and post-natal until the 6th and 11th day after birth). During a two-day session (training and test) the learning and memory of animals (30 days after receiving sodium nitrate) were studied in a step down apparatus. The latency time for coming down from the platform in the test day (S) was used as a criterion for memory. The nitrate oxide metabolites in brain tissue were measured by Miranda method. The nitrite to nitrate recovery and total nitrite measurements were performed using Griess reagents with a spectrophotometer. Results: The oral administration of sodium nitrate (100 mg/L) during pregnancy and lactation until 11 days after birth improved the avoidance memory compared to the control group (P<0.05). Also, sodium nitrate did not change the NO metabolites during those time periods. Conclusion: The oral sodium nitrate in pregnancy and lactation period improves mice avoidance memory without an alternation in nitric oxide metabolites

Effects of Ethanol Preconditioning on Pentylenetetrazole-induced Memory Impairment and Expression of NMDA Receptor NR1 Subunit mRNA in Rat

Abstract Background: Neuronal damage following seizures and epilepsy is one of the main causes of disabilities and mortality worldwide. In recent years, preconditioning has been introduced as a novel strategy for the prevention of brain damage. Preconditioning is a phenomenon in which a minor noxious stimulus protects from a subsequent more severe insult. The aim of present study was to examine the effect of ethanol (Eth) preconditioning on pentylenetetrazole (PTZ)-induced impairment memory in the inhibitory avoidance model. Material and Methods: This study was carried out on 45 adult male Wistar rats (180-200 g). Animals were assigned into five groups: Control, Eth 0.25, Eth 0.5, PTZ and Eth (0.5) +PTZ (n=9, for all groups). Eth-preconditioning was induced 6 days before the injection of PTZ. The animals were tested in a single trial step-through inhibitory test in two sessions (train and test). Then locomotor activity of rats was recorded in the open-field apparatus and NR1 mRNA expression in the hippocampus was measured by real-time PCR technique. Results: One-way ANOVA revealed that the Ethanol preconditioning did not impair inhibitory memory. Further, post-test analyses showed that Ethanol preconditioning significantly prevented from PTZ-induced memory impairment, and increased NR1 subunit mRNA expression in PTZ-induced memory impairment group. In addition, one-way ANOVA for the locomotor activity showed no significant difference between the groups. Conclusion: Our results showed that a pre-conditioning treatment with Ethanol (0.5g/kg/day), 6 days before PTZ-induced memory impairment may provide a kind of neuroprotection in rats

Effects of Hydroalcoholic Extract of Matricaria Recutita L. on Lipid Peroxidation and Nitric Oxide in Pentylenetetrazole-kindled Mice: Ameliorative effects of hydroalcoholic extract of Matricaria recutita L. on epilepsy

Matricaria recutita L. (chamomile) is a well-known medicinal plant. As the main constituents of chamomile, flavonoids such as apigenin, act on benzodiazepine/GABA receptors. This study was designed to determine the protective effect of hydroalcoholic Matricaria recutita (MR) extract (hMRxt) on pentylenetetrazole (PTZ)-induced kindling model and lipid peroxidation in mice. Forty-eight male albino mice (25-30 g) were randomly divided into six groups (n=8). Kindling was induced by 13 PTZ injections (35 mg /kg; i.p.) every other day for 26 days. The seizure score was observed and noted until 30 minutes after the PTZ injection. Finally, the mice were decapitated and their brains were dissected out so as to assess some biochemical factors, namely malondialdehyde (MDA) and nitric oxide metabolites (NOx) in the brain tissue. One-way ANOVA was used for analysis in Prism 6.0. The results showed that hMRxt (400 mg/kg) and valproate (VAP) (150 mg/kg) significantly decreased the progression and duration of seizure induced by PTZ (P &lt;0.001). NOx level in the hMRxt (400 mg / kg), VAP (150 mg / kg) and the combination of hMRxt (50 mg / kg) + VAP (50 mg / kg) groups was significantly reduced compared to the PTZ group. Also, hMRxt (50 and 400 mg/kg) significantly increased the MDA level (P &lt;0.001) compared to PTZ and control groups. This study revealed that hMRxt protects mice against the PTZ-induced epilepsy via NO signaling with no effect on lipid peroxidation