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Toxoplasma gondii has lifelong persistence in the brain and its cysts can affect gene expression and change diverse biological functions of neurons. Many studies indicated T. gondii infection as a risk factor for the development of behavioral changes and neurodegenerative diseases such as Alzheimer's disease (AD), although the etiopathogenetic link between them has not been exactly elucidated. The current study aimed to examine the effects of chronic toxoplasmosis infection with Types I, II, and III strains (RH, PRU, and VEG) alone and in combination on cognitive impairments and neuronal death in the Aß1-42-induced rat model of Alzheimer's disease. In the chronic toxoplasmosis phase, Alzheimer's induction was conducted by injecting Aß1-42 oligomers into the rat brain hippocampus. Behavioral tests were conducted 10 days after the AD induction. Real-time PCR was performed to evaluate T. gondii parasite burden by amplification of the B1 gene. Cytokines IL-1ß, TNF-α, and IL-10 were assayed in brain tissue supernatant using ELISA. Also, histopathological examinations were conducted to calculate inflammatory changes and neuronal death in the brain. Our findings showed that chronic toxoplasmosis infection with PRU reduces cognitive disorders, while the RH strain of T. gondii plays a destructive role and aggravates cognitive impairments in AD. Also, infection with a combination of PRU and VEG strains significantly improved spatial learning and memory impairments in Alzheimer's rat model. Histopathological findings also confirmed the results of behavioral tests, so that in AßPRU and AßPRU + VEG groups, neuronal death and infiltration of inflammatory cells were negligible and significantly less than in Alzheimer's and AßRH groups. Our findings indicate that chronic toxoplasmosis infection with PRU strain alone, also in combination with VEG strain can significantly improve cognitive disorders in AD rats, while RH strain plays a destructive role in AD pathogenesis.
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Enfermedad de Alzheimer , Toxoplasma , Toxoplasmosis , Ratas , Animales , Toxoplasma/genética , Toxoplasmosis/complicaciones , Encéfalo/metabolismo , Citocinas/metabolismoRESUMEN
Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor (CB1R) could affect novel object recognition (NOR) memory in chronically rapid eye movement sleep-deprived (RSD) rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique. The CB1R antagonist rimonabant (1 or 3 mg/kg, i.p.) was administered either at one hour prior to the sample phase for acquisition, or immediately after the sample phase for consolidation, or at one hour before the test phase for retrieval of NOR memory. For the reconsolidation task, rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition, consolidation, and retrieval, but it did not affect the reconsolidation of NOR memory. Rimonabant administration did not affect acquisition, consolidation, and reconsolidation; however, it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings, along with our previous report, would seem to suggest that RSD may affect different phases of recognition memory based on its duration. Importantly, it seems that the CB1R may, at least in part, be involved in the adverse effects of chronic RSD on the retrieval, but not in the acquisition, consolidation, and reconsolidation, of NOR memory.
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Cannabinoides , Memoria , Ratas , Animales , Rimonabant/farmacología , Sueño REM , Receptores de Cannabinoides , Cannabinoides/farmacologíaRESUMEN
Elettaria cardamomum is an aromatic spice (cardamom) native to the humid Asian areas, which contains some compounds with a potential anticonvulsant activity. Various pharmacological properties such as anti-inflammatory, analgesic, antioxidant, and antimicrobial effects have been related to this plant. This research was conducted to examine the probable protective impact of the essential oil and methanolic extract of E. cardamomum against chemically (pentylentetrazole)- and electrically (maximal electroshock)-induced seizures in mice. In addition, neurotoxicity, acute lethality, and phytochemistry of the essential oil and methanolic extract were estimated. The TLC method showed the presence of kaempferol, rutin, and quercetin in the extract, and the concentration of quercetin in the extract was 0.5 µg/mL. The major compounds in the essential oil were 1,8-cineole (45.6â%), α-terpinyl acetate (33.7â%), sabinene (3.8â%), 4-terpinen-4-ol (2.4â%), and myrcene (2.2â%), respectively. The extract and essential oil showed significant neurotoxicity in the rotarod test at the doses of 1.5 g/kg and 0.75 mL/kg, respectively. No mortalities were observed up to the doses of 2 g/kg and 0.75 mL/kg for the extract and essential oil. The essential oil was effective in both the pentylentetrazole and maximal electroshock models; however, the extract was only effective in the pentylentetrazole model. The study suggested that E. cardamomum methanolic extract had no significant lethality in mice. Both the essential oil and methanolic extract showed movement toxicity. Anticonvulsant effects of E. cardamomum were negligible against the seizures induced by pentylentetrazole and maximal electroshock.
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Anticonvulsivantes/farmacología , Elettaria/química , Aceites Volátiles/química , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología , Monoterpenos Acíclicos , Alquenos/análisis , Animales , Monoterpenos Bicíclicos , Ciclohexanoles/análisis , Electrochoque/efectos adversos , Eucaliptol , Masculino , Metanol , Ratones Endogámicos , Monoterpenos/análisis , Aceites Volátiles/toxicidad , Pentilenotetrazol/toxicidad , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológicoRESUMEN
In both human and animal studies, the effect of sleep deficiency on cognitive performances has mostly been studied during adulthood in males, but very little data exist concerning the effects of poor sleep in gonadal hormones-depleted status, such as aging or gonadectomized (GDX) male animal models. The present study investigated the potential modulatory effects of the endogenous male sex hormones on the 48h REM sleep deprivation (SD)-induced cognitive and synaptic impairments by comparing the gonadally intact with castrated male rats, a rodent model of androgen-deprived male animals. The multiple platform method was used for inducing REM-SD and spatial performances were evaluated using Morris water maze (MWM) task. Early long-term potentiation (E-LTP) was measured in area CA1 of the hippocampus and PCR and western blotting assays were employed to assess brain derived neurotrophic factor (BDNF) gene and protein expression in the hippocampus. To reveal any influence of sleep loss on stress level, we also evaluated the plasma corticosterone levels of animals. Regardless of reproductive status, REM-SD significantly disrupted short-term memory and LTP, as well as hippocampal BDNF expression. The corticosterone levels were not significantly changed following REM-SD neither in intact nor in GDX male rats. These findings suggest that depletion of male sex steroid hormones by castration does not lead to any heightened sensitivity of male animals to the deleterious effects of 48h REM-SD on cognitive and synaptic performances.
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Conducta Animal/fisiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Trastornos del Conocimiento , Corticosterona/sangre , Hipocampo/metabolismo , Plasticidad Neuronal/fisiología , Orquiectomía , Memoria Espacial/fisiología , Animales , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/fisiopatología , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Masculino , Ratas , Ratas Sprague-Dawley , Privación de Sueño/complicaciones , Privación de Sueño/metabolismo , Privación de Sueño/fisiopatologíaRESUMEN
The aim of the present study was to investigate the role of the amygdala in the potentiative effect of minocycline, a semisynthetic tetracycline antibiotic, on morphine analgesia in male Wistar rats. We also examined the involvement of the amygdala µ-opioid and N-methyl-D-aspartate (NMDA) receptors in the minocycline-induced potentiation of morphine analgesia. Intraperitoneal administration of morphine (3-9 mg/kg) induced analgesia in a tail-flick test. Bilateral intra-amygdala injection of minocycline (10-20 µg/rat) enhanced the analgesic response of an ineffective dose of morphine (3 mg/kg). Injection of a higher dose of minocycline into the amygdala also induced analgesia. Moreover, bilateral intra-amygdala injection of naloxone (0.5-1.5 µg/rat) reversed minocycline-induced potentiation of morphine analgesia. Pretreatment of animals with NMDA (0.01-0.1 µg/rat, intra-amygdala) also inhibited the potentiative effect of minocycline on morphine response. Bilateral intra-amygdala injection of the same doses of naloxone or NMDA plus morphine had no effect on the tail-flick latency in the absence of minocycline. It can be concluded that the amygdala has a key role in the potentiative effect of minocycline on morphine analgesia. In addition, amygdala opioidergic and glutamatergic mechanisms may be involved, probably through µ-opioid and NMDA receptors, in the modulation of the minocycline-induced potentiation of morphine analgesia in the tail-flick test.
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Amígdala del Cerebelo/efectos de los fármacos , Analgésicos/farmacología , Minociclina/farmacología , Morfina/farmacología , Dolor/tratamiento farmacológico , Amígdala del Cerebelo/metabolismo , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Agonistas de Aminoácidos Excitadores/farmacología , Calor , Inyecciones Intraperitoneales , Masculino , N-Metilaspartato/farmacología , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Dolor/metabolismo , Dimensión del Dolor , Distribución Aleatoria , Ratas Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores Opioides mu/metabolismoRESUMEN
Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects of psychostimulants on dopamine system of the brain. Moreover, aging may affect sleep and drug addiction. This study, therefore, set out to assess the effects of methamphetamine (METH) and REM sleep deprivation (RSD) on locomotor activity, anxiety-like behavior and spatial memory in adult and adolescent rats. Adult and adolescent male Wistar rats received a neurotoxic METH regimen; four subcutaneous injections of 6 mg/kg, at 2 h intervals. Five days later, the animals underwent a 48-h RSD episode using the multiple platforms method. They were then examined using the open field (OF), elevated plus maze (EPM) and Y-maze tasks. We found that the METH and RSD paradigms showed synergistic effects to increase locomotion and risk-taking behavior in both adult and adolescent animals, while only adolescent rats revealed RSD-induced anxiety-like behavior. Moreover, adolescent animals revealed greater sensitization for vertical activity following METH plus RSD episode. In addition, METH and RSD paradigms revealed synergistic effects to impair spatial working memory, but neither METH nor RSD alone affected performance of animals in the Y-maze task. Our findings may indicate that there are important relationships between METH and RSD to induce hyperlocomotion, risk-taking behavior and spatial memory impairment, particularly in adolescent animals. Moreover, it seems that adolescent rats may be more susceptible to anxiety-like behavior and hyperlocomotion than adults.
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Ansiedad , Estimulantes del Sistema Nervioso Central , Aprendizaje por Laberinto , Metanfetamina , Ratas Wistar , Privación de Sueño , Animales , Metanfetamina/farmacología , Masculino , Estimulantes del Sistema Nervioso Central/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Ratas , Memoria Espacial/efectos de los fármacos , Memoria Espacial/fisiología , Locomoción/efectos de los fármacos , Locomoción/fisiología , Sueño REM/efectos de los fármacos , Sueño REM/fisiología , Actividad Motora/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Envejecimiento/fisiología , Envejecimiento/efectos de los fármacosRESUMEN
BACKGROUND: The Modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) was developed with the primary objective of evaluating food addiction (FA). The present study aimed to undertake the translation, pilot testing, and evaluation of the psychometric properties of the mYFAS 2.0 within the Persian-speaking population. METHODS: The transcultural adaptation of the mYFAS 2.0 to the Persian language was conducted. Data collection was carried out through an anonymous online questionnaire. Participants completed the Persian versions of the mYFAS 2.0, Binge Eating Scale (BES), Barratt Impulsivity Scale (BIS-11), and Connor-Davidson Resilience Scale (CD-RISC). The assessment encompassed the evaluation of internal consistency reliability, factor structure, as well as convergent and discriminant validity of the aforementioned questionnaires. RESULTS: Confirmatory factor analysis revealed that the single-factor model of the Persian translation of mYFAS 2.0 performed satisfactorily, with comparative fit index (CFI) and Tucker-Lewis index (TLI) values exceeding 0.95, standardized root mean square residual (SRMR) less than or equal to 0.09, and root mean square error of approximation (RMSEA) below 0.03. The internal consistency and composite reliability of the mYFAS 2.0 were favorable in the entire sample, as well as in both male and female groups, with alpha (α) values of 0.83, ordinal alpha (αord) of 0.93, and composite reliability (CR) of 0.86. Additionally, significant relationships were observed between the total score of BES (r = 0.59, p < 0.001), BIS-11 (r = - 0.16, p < 0.001), and CD-RISC (r = 0.22, p < 0.001) with mYFAS 2.0-diagnosed FA presence, severity, and symptom count. CONCLUSIONS: The Persian version of the mYFAS 2.0 exhibited satisfactory psychometric properties.
In this study, researchers developed a Persian version of the Modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) to assess food addiction in Persian-speaking individuals. They translated and tested the scale's reliability and validity through an online survey with 9606 Persian speaking participants. The results showed that the Persian mYFAS 2.0 performed well, with a reliable single-factor model. The internal consistency and reliability were good across the entire sample and in both male and female groups. The relationships between mYFAS 2.0 and other scales measuring binge eating, impulsivity, and resilience were significant. The findings suggest that the Persian version of mYFAS 2.0 is a reliable tool for assessing food addiction in the Persian-speaking population. The study used statistical analyses like confirmatory factor analysis, indicating the scale's robustness. Overall, the psychometric properties of the Persian mYFAS 2.0 were satisfactory, providing a valuable instrument for researchers and healthcare professionals studying and addressing food addiction in this population. The study contributes to cross-cultural research and enhances our understanding of food addiction in diverse linguistic communities.
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Background: Methamphetamine (MA), is a widely abused synthetic psychostimulant that leads to irreversible brain damage manifested as cognitive impairments in humans and animals. The novel object recognition (NOR) task is a commonly used behavioral assay for the investigation of non-spatial memory in rodents. This test is based on the natural tendency of rodents to spend more time exploring a novel object than a familiar one. NOR test has been used in many studies investigating cognitive deficits caused by MA in rodents. The objective of the present study was to review neurobiological mechanisms that might be responsible for MA-induced NOR alterations. Methods: A PubMed search showed 83 publications using novel object recognition and methamphetamine as keywords in the past 10 years. Findings: The present study revealed different MA regimens cause recognition memory impairment in rodents. In addition, it was found that the main neurobiological mechanism involved in MA-induced recognition deficits is the dysfunction of monoaminergic systems. Conclusion: NOR is a useful test to assess the cognitive functions following MA administration and evaluate the efficacy of new therapeutic agents in MA-addicted individuals.
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Mood disorders are among the common mental disorders worldwide. Because of the persistence of cytomegalovirus (CMV) in the body and nervous system, this virus can be activated when the immune system is weakened and continues to exert its destructive effects throughout life. This study aimed to investigate the seroprevalence and association of human cytomegalovirus with mood disorders. Eligible articles were extracted using online international databases Science Direct, Medline, Web of Science, Scopus, and Google Scholar between 2000 and 2023. After quality assessment and specific inclusion and exclusion criteria, a total of eight eligible articles were included in the meta-analysis. Our finding showed that the seropositivity of CMV in mood disorders was 51.6% (95% CI; 42.8-60.4). There were statistical differences between mood disorders and control groups regarding the seropositivity of CMV 1.327% (95% CI; 13.27-10.45). The results of the publication bias using the Egger test confirmed no publication bias in each sub-group. The results of this meta-analysis study demonstrated that CMV infection might have associations with the incidence of mood disorders. Furthermore, we found that there were statistical differences between mood disorders and control groups regarding the seropositivity of CMV.
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Introduction: Coronavirus-2019 (COVID-19) spreads rapidly worldwide and causes severe acute respiratory syndrome. The current study aims to evaluate the relationship between the whole-brain functional connections in a resting state and cognitive impairments in patients with COVID-19 compared to the healthy control group. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) and Montreal cognitive assessment (MoCA) data were obtained from 29 patients of the acute stage of COVID-19 on the third day of admission and 20 healthy controls. Cross-correlation of the mean resting-state signals was determined in the voxels of 23 independent components (IC) of brain neural circuits. To assess cognitive function and neuropsychological status, MoCA was performed on all participants. The relationship between rs-fMRI information, neuropsychological status, and paraclinical data was analyzed. Results: The COVID-19 group got a lower mean MoCA score and showed a significant reduction in the functional connectivity of the IC14 (P<0.001) and IC38 (P<0.001) regions compared to the controls. The increase in functional connectivity was observed in the COVID-19 group compared to the controls at baseline in the default mode network (DMN) IC00 (P<0.001) and dorsal attention network (DAN) IC08 (P<0.001) regions. Furthermore, the alternation of functional connectivity in the mentioned ICs was significantly correlated with the mean MoCA scores and inflammatory parameters, i.e. erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Conclusion: Functional connectivity abnormalities in four brain neural circuits are associated with cognitive impairment and increased inflammatory markers in patients with COVID-19. Highlights: The patients with coronavirus-2019 (COVID-19) got a lower mean Montreal cognitive assessment (MoCA) score.The patients with COVID-19 showed significant reduction in the functional connectivity of the IC14 and IC38 regions.The patients with COVID-19 showed significant increase of functional connectivity in the default mode network (DMN) IC00 and dorsal attention network (DAN) IC08 regions.Alternation of functional connectivity was significantly correlated with the mean MoCA scores and ESR and CRP. Plain Language Summary: The researcher aimed at assessing cognitive impairments and investigating the whole-brain functional connectivity using resting state fMRI in patients with COVID-19 compared with healthy control group. The result showed That COVID-19 group got a lower mean cognitive score and showed a significant reduction in the functional connectivity of the IC14 and IC38 regions of brain compared with controls. Also, the increase of functional connectivity was observed in the COVID-19 group compared with controls at baseline in the default mode network (DMN) and dorsal attention network (DAN) regions of brain. Moreover, Functional connectivity abnormalities in four brain neural circuits associated with cognitive impairment and increased inflammatory markers in patients with COVID-19.
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Introduction: It has long been known that Methamphetamine (MA), as a psychostimulant, leads to long-lasting cognitive deficits. Previous studies have shown that lithium, a mood stabilizer, could facilitate cognitive ability in most of brain diseases. In current study the effects of lithium on spatial memory, hippocampal apoptosis and brain edema in METH-exposed rats are investigated. Methods: The present study 32 Wistar rats were used to examine the effects of lithium on spatial memory by the Morris water maze, hippocampal apoptosis using the TUNEL assay, and brain edema following MA administrations. Results: The findings indicated that treatment with lithium significantly ameliorated spatial learning and memory impairment in MA-treated rats. In addition, the findings showed that treatment with lithium significantly reduced brain edema and apoptosis in the CA1 neurons in MA -exposed rats. Conclusion: The results show that treatment with lithium can partially ameliorate the MA-induced neurocognitive deficits in rats, which may be related to its protective effect in the hippocampus.
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We aimed to determine whether REM sleep deprivation (RSD) affects extinction and reinstatement of methamphetamine (METH) reward memory in male rats and also to evaluate the possible role of dopamine D1-like and D2-like dopamine (DA) receptors in these processes. Male rats were trained to acquire METH-induced place preference (2 mg/kg, i.p.). METH reward memory was then reinstated following a 10-day extinction period. The animals underwent a 72-hour sleep deprivation episode by multiple platforms method (in separate groups), either before the extraction or before the reinstatement of METH reward memory. The animals received SCH 23390 (0.01 or 0.05 mg/kg, i.p.) or sulpiride (20 or 60 mg/kg, i.p.) as antagonists of D1-like and D2-like DA receptors, respectively, either immediately following each daily extinction session or before the reinstatement of METH-seeking behavior. The RSD episode postponed extinction and facilitated reinstatement of METH reward memory. Administration of SCH 23390, but not sulpiride, facilitated METH extinction and decreased reinstatement of the extinguished METH-seeking behavior. Moreover, locomotor activity was not affected by METH and/or the RSD paradigm. The results would seem to suggest that the D1-like, but not the D2-like, DA receptors may be involved in the extinction and reinstatement of the extinguished METH reward memory in RSD animals. Nonetheless, more investigations are needed to elucidate the exact mechanisms involved.
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Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Metanfetamina/farmacología , Trastorno de la Conducta del Sueño REM/metabolismo , Receptores de Dopamina D1/metabolismo , Privación de Sueño/metabolismo , Animales , Benzazepinas/farmacología , Condicionamiento Psicológico/efectos de los fármacos , Dopaminérgicos/farmacología , Extinción Psicológica/efectos de los fármacos , Locomoción/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Ratas , Ratas Wistar , Receptores de Dopamina D2/metabolismo , Recompensa , Sueño REM , Sulpirida/farmacologíaRESUMEN
Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C) is one of the most important genes associated with schizophrenia. In this study, 45 male Wistar rats were divided into 5 groups of saline, control, ketamine, clozapine, and risperidone. Animals in ketamine, risperidone, and clozapine groups received ketamine (30 mg/kg-i.p.) for 10 days. After the last injection of ketamine, we started injecting clozapine (7.5 mg/kg-i.p.), risperidone (1 mg/kg-i.p.), up to 28 days. Twenty-four hours after the last injection, open field, social interaction, and elevated plus-maze tests and gene expression in hippocampus were performed. The results of the social interaction test revealed a significant decrease in cumulative time with ketamine, compared with the saline group, and an increase with clozapine and risperidone compared with the ketamine group. Moreover, results from the elevated plus-maze test demonstrated a critical decrease in open arm time and increase in close arm time with ketamine compared with saline, as well as increased in open arm time with risperidone compared with ketamine. Further results revealed a significant increase in rearing and grooming with ketamine compared to saline, as well as a decrease with risperidone and clozapine compared to ketamine. There were no significant differences in CACNA1C gene expression between groups in the rat hippocampus. In brief, the results of this study indicated that clozapine and risperidone could partially improve cognitive impairments in the rat. However, our findings demonstrated that this treatment is not related to CACNA1C gene expression.
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Antipsicóticos/farmacología , Canales de Calcio Tipo L/metabolismo , Clozapina/farmacología , Hipocampo/efectos de los fármacos , Risperidona/farmacología , Esquizofrenia/metabolismo , Animales , Canales de Calcio Tipo L/genética , Cognición , Antagonistas de Aminoácidos Excitadores/toxicidad , Hipocampo/metabolismo , Hipocampo/fisiopatología , Ketamina/toxicidad , Masculino , Aprendizaje por Laberinto , Ratas , Ratas Wistar , Esquizofrenia/etiología , Esquizofrenia/fisiopatología , Conducta SocialRESUMEN
Methamphetamine (METH) has been reported to induce social and recognition memory impairment. Evidence suggests that the cannabinoid system has an important modulatory role in cognitive processing and social interaction. Nonetheless, no previous study has investigated the probable role of the cannabinoids system on METH-induced deficits of novel object recognition (NOR) memory and social interaction. Adult male rats were given a neurotoxic METH regimen (four injections of 6 mg/kg, s.c, at 2 h intervals). One week later, they were examined for either NOR or social interaction in different groups. The cannabinoid type 1 receptor (CB1R) antagonist rimonabant (1 or 3 mg/kg, i.p.) improved METH-induced impairment of the acquisition, consolidation, and retrieval, but not reconsolidation, of NOR and also METH-induced impairment of social behavior. Administration of the CB1R agonist WIN 55,212-2 (WIN; 3 or 5 mg/kg, i.p.) did not affect memory deficits or social behavior impairment induced by METH. Our findings may indicate that METH neurotoxicity impairs social and recognition memory. On the other hand, the CB1R antagonist rimonabant, but not the CB1R agonist WIN, prevented these negative effects of METH neurotoxicity. Thus, it seems that the CB1R can be targeted to prevent the adverse effects of METH on cognition and social behavior, at least at experimental levels.
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Cannabinoides , Metanfetamina , Síndromes de Neurotoxicidad , Animales , Antagonistas de Receptores de Cannabinoides/farmacología , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/prevención & control , Metanfetamina/toxicidad , Ratas , Receptor Cannabinoide CB1 , RimonabantRESUMEN
Methamphetamine (METH) may cause longâlasting neurotoxic effects and cognitive impairment. On the other hand, the ovarian hormones estrogen and progesterone have neuroprotective effects. In the current study, we aimed to examine the effects of estrogen and progesterone on anxietyâlike behavior and neuronal damage in METHâexposed ovariectomized (OVX) rats. Three weeks after ovariectomy, the animals received estrogen (1 mg/kg, i.p.), or progesterone (8 mg/kg, i.p.), or estrogen plus progesterone (with the same doses), or vehicle during 7 consecutive days (days 22-28). On day 28, OVX rats were exposed to a singleâday METH regimen (6 mg/kg, four s.c. Injections, with 2 h interval) 30 min after the hormone treatment. The next day (on day 29), the animals were assessed for anxietyârelated behaviors using the open field and elevated plusâmaze tasks. The animals were then sacrificed and brain water content, cell apoptosis and expression of IL-1ß were evaluated. The findings showed that treatment with estrogen or progesterone alone in METHâexposed rats significantly improved hyperthermia, anxietyâlike behavior, neuronal damage, and inflammation in the CA1 area. Also, treatment with estrogen plus progesterone improved hyperthermia and brain edema. Taken together, the findings suggest that treatment with ovarian hormones can partially prevent hyperthermia and anxietyârelated behaviors induced by METH in OVX rats, which could be accompanied by their neuroprotective effects in the hippocampus.
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Ansiedad/metabolismo , Encéfalo/metabolismo , Estrógenos/uso terapéutico , Metanfetamina/toxicidad , Ovariectomía/efectos adversos , Progesterona/uso terapéutico , Animales , Ansiedad/inducido químicamente , Ansiedad/prevención & control , Encéfalo/efectos de los fármacos , Encéfalo/patología , Estimulantes del Sistema Nervioso Central/toxicidad , Estrógenos/farmacología , Femenino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Ovario/metabolismo , Progesterona/farmacología , Ratas , Ratas WistarRESUMEN
A survey of the literature indicates that both rapid eye movement sleep deprivation (RSD) and activation of cannabinoid CB1 receptor (CB1R) may impair novel object recognition (NOR) memory in rodents. To our knowledge, so far, no previous study has investigated the probable effects of RSD on the different phases of NOR memory. Moreover, far too little attention has been paid to the potential role of the CB1R in the effects of RSD on object memory. Therefore, the major objective of this study was to investigate the probable role of the CB1R in the acquisition, consolidation, retrieval, and reconsolidation of NOR memory in the RSD rats. A 12-h paradigm of RSD using the multiple platform method did not affect acquisition, but it impaired the consolidation, retrieval, and reconsolidation of NOR memory. Administration of the CB1R antagonist rimonabant (1 or 3â¯mg/kg, i.p.) did not have significant effects on the acquisition and reconsolidation, but it improved RSD-induced impairment of the consolidation and retrieval of object memory, especially at the dose of 3â¯mg/kg. In addition, the RSD paradigm did not affect the levels of plasma corticosterone as an important marker of stress in rat. The results revealed that RSD may have different effects on the different phases of NOR memory which may not be attributable to the effects of stress. Our findings would seem to suggest that the CB1R can be targeted to, at least partially, modulate the adverse effects of RSD on the process of NOR memory.
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Prueba de Campo Abierto/fisiología , Receptor Cannabinoide CB1/fisiología , Reconocimiento en Psicología/fisiología , Privación de Sueño/fisiopatología , Animales , Antagonistas de Receptores de Cannabinoides/farmacología , Corticosterona/sangre , Prueba de Campo Abierto/efectos de los fármacos , Ratas , Receptor Cannabinoide CB1/antagonistas & inhibidores , Reconocimiento en Psicología/efectos de los fármacos , Rimonabant/farmacología , Estrés Psicológico/sangreRESUMEN
BACKGROUND: Early life stress (ELS) models such as maternal deprivation (MD) are used to investigate behavioral changes in rodents under stressful situations. MD is a situation in which rat pups are separated from the dam; MD has different paradigms. The purpose of this research is to evaluate the effects of maternal deprivation on anxiety, depression, and empathy in adult Wistar rats. MATERIALS AND METHODS: MD was applied to pups as per specifically designed protocol to compare rats of the control group with maternal deprivation rats and also the group, which faced novel objects. Each group consisted of eight rats. In this study, separation started from postnatal day (PND) 14 for various periods up to PND 60. EPM test was undertaken to measure anxiety; moreover, FST was used to indicate levels of depression. Also, changes in the empathy ratio were also demonstrated. One-way analysis of variance (ANOVA), Tukey's post hoc analysis, and t-test were applied to analyze the results. RESULTS: MD-treated rats showed a significant decrease in anxiety and empathy indexes compared with those in the control group (P<0.05). However, MD significantly increased depression in both male and female rats (P<0.05). Finally, exposure to novel objects decreased depression but did not have any effect on anxiety and empathy levels in MD rats (P<0.05). CONCLUSION: ELS may lead to various states of mood and behavior in adulthood. According to the findings of this study, depression increases due to MD, though both anxiety and empathy decrease in both male and female Wistar rats. Moreover, exposure to novel objects decreases depression, while anxiety and empathy do not change significantly with exposure to novel objects.
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BACKGROUND: Methamphetamine (METH) as a synthetic psychostimulant is being increasingly recognized as a worldwide problem, which may induce memory impairment. On the other hand, it is well established that naloxone, an opiate antagonist, has some beneficial effects on learning and memory. The present research aimed at evaluating naloxone effects on spatial learning and memory impairment triggered by a neurotoxic regimen of METH in male rats. MATERIALS AND METHODS: The animals received the subcutaneous (sc) regimen of METH (4×6 mg/kg at 2-h intervals), intraperitoneal (ip) naloxone (4×1 mg/kg at 2-h intervals), or normal saline at four events. The Nal-METH group of rats received four naloxone injections (1 mg/ kg, ip) 30 min before each METH injection (6 mg/kg, sc) at 2-h intervals. Seven days later, they were evaluated for spatial learning and memory in the Morris Water Maze (MWM) task. RESULTS: METH regimen induced hyperthermia, as well as a poor performance, in the acquisition and retention phases of the task, indicating spatial learning and memory impairment compared to the controls. Naloxone administration (1 mg/kg, ip) before each METH injection led to significant attenuations of both hyperthermia and METH adverse effects on the rat performance in the MWM task. CONCLUSION: The results revealed that pretreatment with the opiate antagonist naloxone could prevent METH adverse effects on body temperature and memory performance. It seems that the opioidergic system and hyperthermia may, at least partially, be involved in METH effects on spatial memory.
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Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition which develops in 6-8% of the general population. Current standard pharmacological treatments for PTSD cannot be widely used due to having various side effects. Nowadays, various pharmacological properties have been related to Elettaria cardamomum L. (family of Zingiberaceae). The present study aims to evaluate the efficacy of E. cardamomum methanolic extract on anxiety-like behavior in a rat model of PTSD. Adult male Wistar rats (200-250gr) were used in this study. The rats underwent single prolonged stress (SPS) or control and intraperitoneally received either saline or different dosages (200, 400, and 800mg/kg) of E. cardamomum methanolic extract before and after stress sessions. Moreover, open field, elevated plus-maze, and rotarod tests were used to evaluate locomotion and anxiety-like behavior in the rats. Findings demonstrated that E. Cardamomum methanolic extract, particularly at the dose of 400mg/kg, significantly (P<0.05) improved anxiety-like behavior in a rat model of PTSD, as examined by the open field, elevated plus-maze, and rotarod tests. Administration of E. cardamomum methanolic extract after stress might help to prevent the formation of anxiety-like behavior in the animals. However, further studies are requiredto clarify the exact mechanisms involved.
Asunto(s)
Ansiedad/tratamiento farmacológico , Elettaria/química , Extractos Vegetales/farmacología , Trastornos por Estrés Postraumático/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Locomoción/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
BACKGROUND: Methamphetamine (METH) is one of the most popular psychostimulants which produce long lasting learning and memory impairment. Previous studies have indicated that estrogen and progesterone replacement therapy attenuate cognitive impairment against a wide array of neurodegenerative diseases. Present study was designed to figure out the effects of estrogen, progesterone alone or in combination, on early long-term potentiation (E-LTP) at the cornu ammonis (CA1) area of the hippocampus in METH-exposed ovariectomized (OVX) rat. METHODS: Twenty-one days after ovariectomy, the OVX rats received vehicle, estrogen [1 mg/kg, intraperitoneal (IP)] or progesterone (8 mg/kg, IP) and co-administration of estrogen plus progesterone during 14 consecutive days. On the 28th day, animals were exposed to neurotoxic METH regimens [four injections 6 mg/kg, subcutaneous (SC), 2 h intervals] 30 min after the hormones replacement. Finally, we investigated the effect of those ovarian hormones on synaptic plasticity using in vivo extracellular recording in the CA1 area of the hippocampus 2 days after last treatment. FINDINGS: The findings showed that the induction and maintenance phase of E-LTP was impaired in the METH exposed animals compared to the saline group. Data from this study demonstrated that treatment with estrogen and progesterone showed a significant facilitation for induction and enhancement of the maintenance of LTP in animals that received METH. In addition, co-administration of estrogen plus progesterone did not significantly affect the hippocampal synaptic plasticity in METH-exposed OVX rats in comparison with METH-exposed animals that received vehicle injections. CONCLUSION: The present findings provide new insight about treatment with ovarian hormones on synaptic plasticity deficits induced by METH.