Introduction: This study investigates the effects of cannabinoid agonist WIN55-212-2 on acquisition and consolidation phases of the fear memory extinction and also on anxiety and motor activity. Methods: In this study, we used SPS & S model to induce post-traumatic stress disorder. One week after SPS, to establish a conditioned fear memory, rats received an electric foot shock within shock chamber. After 24 h, for extinction training, the rats were placed back to the chamber for 9 min, without receiving any shock. In 3 consecutive days and on days 17, 24 and 37, extinction tests were carried out and the freezing behavior was evaluated. Thirty minutes before the first three extinction tests, animals received IP injections of WIN or vehicle. Anxiety-like behavior examined with elevated plus-maze and motor activity with open field, 32 days after conditioning. Results: Exaggerated and continued conditioned fear memory observed in SPS & S group compared with shock group. IP injection of a 0.25 mg/kg dose of WIN before extinction training led to reducing fear responses in animals. Conclusion: IP injection of WIN increased acquisition or consolidation of fear memory extinction. SPS & S caused anxiety and this effect improved by the agonist (0.25 mg/kg).
AUTHOR KEYWORDS: Cannabinoids; Extinction; Post-traumatic stress disorder; Win 55212-2 INDEX KEYWORDS: 2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo[1,2,3 de][1,4]benzoxazine, animal experiment; animal model; anxiety; Article; conditioning; controlled study; drug effect; elevated plus maze test; fear; footshock; male; memory; memory consolidation; motor activity; nonhuman; open field test; posttraumatic stress disorder; rat; reinforcement
Introduction: Excessive olivo-cerebellar burst-firing occurs during harmaline-induced tremor. We hypothesized that antiglutamatergic agents would suppress harmaline tremor. From this point of view, the aim of the present study was to investigate the effects of riluzole on harmaline-induced tremor in rat. Methods: Four groups of Wistar rats weighing 80-100 g were injected with harmaline (30 mg/ kg i.p.) for inducing experimental tremors. The rats in group 1 served as control, whereas the animals in groups 2, 3 and 4 were also given riluzole intraperitonealy at doses of 2, 4 and 8 mg/ kg 30 min before and 90 min after harmaline administration. The onset latency, intensity and duration of tremor were recorded. Results: The results of this study demonstrated that riluzole could significantly increase latency period, and reduce duration and intensity of tremor. Discussion: It is concluded that pretreatment of riluzole can ameliorate harmaline-induced tremor in rats.
AUTHOR KEYWORDS: Harmaline; Rat; Riluzole; Tremor INDEX KEYWORDS: harmaline; riluzole, animal experiment; animal model; article; controlled study; disease duration; disease severity; drug effect; drug efficacy; experimental study; latent period; male; nonhuman; rat; treatment response; tremor; Wistar rat
Objective(s): Stress induces many homeostatic aberrations which are followed by lifelong allostatic responses. Epilepsy is developed or influenced by different environmental factors, i.e. prenatal stress which makes many contradictory developmental changes in seizure threshold and intensity. We investigated the potential seizure response of the rat offspring to prenatal stress; the stress which was applied to their mothers. Materials and Methods: Nine day heterogeneous sequential stress (HSS) model was used before and during the first and before the second pregnancy. The kindling was induced using 13 IP injections of pentylenetetrazol (PTZ) every 48 hr to adult male Wistar rat's offspring. Results: The results of the present study demonstrated that, before pregnancy stress decreased the rate of kindling (P<0.05) in the offspring, while stress which was applied during pregnancy completely prevented kindling (P <0.001). Further, their convulsive latency was increased and tonic clonic seizure duration was decreased. In contrast, previous pregnancy and between pregnancies stress could not change kindling process. Although maternal separation stress did not change kindling development, it could increase convulsive intensities by elongating the duration of seizures (P<0.05) and reducing convulsion latency (P <0.05). Conclusion: It is concluded that stress detrimental effects could be prevented by stress which was applied around first pregnancy; however this beneficial effect is weakened by before second pregnancy stress.
Introduction: Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. Lateral hypothalamus, as the main niche of orexin neurons with extensive projections, is involved in sleep and wakefulness and so it affects the excitability of the brain. Therefore, we investigated whether lateral hypothalamic area (LHA) inactivation or orexin-A receptor blocking could change convulsive behavior of acute and kindled PTZ treated animals and if glutamate has a role in this regard. Methods: Kindling was induced by 40 mg/kg PTZ, every 48 hours up to 13 injections to each rat. Three consecutive stages 4 or 5 of convulsive behavior were used to ensure kindling. Lidocaine was injected stereotaxically to inactivate LHA, unilaterally. SB334867 used for orexin receptor 1 (OX1R) blocking administered in CSF. Results: We demonstrated that LHA inactivation prevented PTZ kindling and hence, excitability evolution. Hippocampal glutamate content was decreased due to LHA inactivation, OX1R antagonist infusion, lidocaine injection and kindled groups. In accordance, OX1R antagonist (SB334867) and lidocaine injection decreased PTZ single dose induced convulsive behavior. While orexin-A i.c.v. infusion increased hippocampal glutamate content, it did not change PTZ induced convulsive intensity. Discussion: It is concluded that LHA inactivation prevented kindling development probably through orexin receptor antagonism. CSF orexin probably acts as an inhibitory step on convulsive intensity through another unknown process.
Objective: This research study is an attempt to examine whether the administration of ethanol after memory reactivation would modulate subsequent expression of memory in rats. Additionally, we examined whether this administration alters the density of Cornu Ammonis (CA)1 and CA3 pyramidal and dentate gyrus (DG) granule cells. Materials and Methods: In this experimental study, adult male Wistar rats (200-300 g) were trained in a fear conditioning system using two 1 second, 0.6 mA shocks with an interval of 180 seconds. Twenty four hours later rats were returned to the chamber for 120 seconds. Immediately after reactivation they were injected with ethanol (0.5, 1, 1.5 mg/kg) or saline. 1, 7 and 14 days after reactivation, rats were returned to the context for 5 minutes. Seconds of freezing (absence of all movement except respiration) were scored. In the second experiment (described in the previous paragraph), after test 1, animals were anesthetized with sodium pentobarbital and perfused transcardially with phosphate buffer (10 minutes) and 4% paraformaldehyde (15 minutes). The brains were postfixed in phosphate-buffered 4% paraformaldehyde (24 hours) and 30% sucrose. 10-μm sections were stained with cresyl violet. Data were analyzed by 1-and 2-way ANOVA for repeated measurements by means of SPSS 16.0. Tukey's post hoc test was performed to determine the source of detected significant differences. P <0.05 were considered significant. Data are presented as mean ± SEM. Results: Findings from the first experiment indicated that ethanol at a dose of 1.5 mg/kg significantly impaired recall of memory only in the first test. The density of CA1 and CA3 pyramidal and DG granule cells in the ethanol group was decreased (p< 0.01) compared with control group respectively 43.7%, 35.8%, and 37.8. Conclusion: The data demonstrate that ethanol exposure impairs post retrieval processes. Moreover, ethanol decreases the density of CA1, CA3 and DG cells. Presumably it would be a correlation between our behavioral and histological results.
Introduction: This study examined the effects of administration of subcutaneous β-estradiol on PTSD-like symptoms (the enhanced conditioned fear response, CFR) that induced by a single-prolonged stress (SPS) and shock in rats. Methods: Adult male Wistar rats were exposed to SPS procedure: restraint for 2 h, forced swim for 20 min, and ether anesthesia. Then the rats were placed in fear conditioning system and received 1 mA electric foot shock for 4 s. Following, stressed rats injected with β-estradiol (600 μxg/kg) or sesame oil. For CFR testing, 24 h later animals were re-exposed to the shock chamber for 3-min without further shock application. Percent of freezing was scored. Following testing, the animals were anesthetized and their brains were removed for histological examination (cell count) of the hippocampus that stained with cresyl violet. Results: Our results indicated that rats who received electric shock after the SPS exhibited the CFR. β-estradiol significantly reduced the CFR in the SPS rats as compared with control rats. No significant differences were found in cell count in different regions of the hippocampus between experimental groups. Discussion: Our findings indicated that β-estradiol administration after SPS prevents the enhanced CFR in an animal model of PTSD, suggesting a possible role for (3-estradiol in the prevention of PTSD.
Objective(s): The purpose of this study was to investigate the role of oxidative stress in Purkinje cell neurotoxicity of ethanol-treated rat. Materials and Methods: Male rat pups 4-day-old was used in this study. Ethanol was administered to rat pups at a dose of 6 g/kg from postnatal days (PDs) 4 to 5. Pups were killed 90 min after the second alcohol treatment on PD 5 by decapitation and the brain was immediately removed. The cerebellum was dissected for analyzing the oxidative stress parameters and histological study. The activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in vermis of cerebellum were assayed. Thiobarbituric acid reactive substances (TBARS) levels were also measured as a marker of lipid peroxidation. Results: Administration of ethanol significantly increased TBARS levels in the cerebellum compared to control pups (P< 0.01). The treated pups with ethanol exhibited a marked decrease in the GPx activity (P< 0.01) whereas, in spite of decrease in the activities of SOD and CAT, when compared to control, there were not significant differences. The spherical cell bodies of Purkinje cells in control rats are aligned nicely between the granular and molecular layers. In ethanol treated pups, Purkinje cells scattered within the Purkinje cell layer and shrinkage of the cell somata is seen. Conclusion: The results of the present work demonstrated that ethanol exposure during the vulnerable window could increase TBARS levels (lipid peroxidation) and decrease GPx levels in pup's cerebellum. Also, the results confirmed ethanol-induced microencephaly, cerebellar Purkinje cell loss. These findings suggest that Purkinje cell loss is, in part through decrease in the activity of GPx and increase of lipid peroxidation in the rat cerebellum.
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