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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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Ansiedade , Estimulantes do Sistema Nervoso Central , Aprendizagem em Labirinto , Metanfetamina , Ratos Wistar , Privação do Sono , Animais , Metanfetamina/farmacologia , Masculino , Estimulantes do Sistema Nervoso Central/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Sono REM/efeitos dos fármacos , Sono REM/fisiologia , Atividade Motora/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Envelhecimento/fisiologia , Envelhecimento/efeitos dos fármacosRESUMO
BACKGROUND: Smart phone use has become a part of people's everyday life. However, when the lack of using the smart phone to establish and maintain electronic communication is related to psychological distress, such a behavior may be considered a modern-age phobia, or nomophobia (no mobile phone phobia). The aims of the present study were to investigate among a sample of young adults the associations between scores for nomophobia and symptoms of depression, anxiety, stress, insomnia, and obsessive-compulsive disorders. METHODS: A total of 537 students (mean age: 25.52 years; 42.3% females) participated in the study. They completed a booklet of self-rating questionnaires covering sociodemographic information and symptoms of nomophobia, depression, anxiety, stress, insomnia, and obsessive-compulsive disorders. RESULTS: Higher scores for nomophobia were associated with higher scores for depression, anxiety, and stress, but not with scores for insomnia and obsessive-compulsive disorders. The regression model confirmed that symptoms of anxiety predicted nomophobia. CONCLUSIONS: The present results support the assumption that nomophobia appears to be a mood disturbance related to stronger associations with symptoms of anxiety and, to a lesser extent, with symptoms of depression and stress. By contrast, nomophobia appeared to be unrelated to insomnia and symptoms of obsessive-compulsive disorders.
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Sleep deficiency is known as an important risk factor for relapse to drug abuse, especially for the powerful psychostimulant methamphetamine (METH). On the other hand, both drug addiction and sleep neurobiology are affected by sex hormones. We, therefore, aimed to examine the probable effects of sleep deprivation (SD) on methamphetamine (METH) reward memory in male and female rats. Moreover, we asked if sex hormones influence the effects of SD on METH reward memory. Adult male and female Wistar rats were divided into two main groups, sham and gonadectomized groups. Three weeks later, they were conditioned to receive METH (2 mg/kg, i.p.) in the conditioned place preference. METH reward memory was then reinstated following a 10-day extinction period. SD was induced for 72 h, either before or after extinction, in different groups. In gonadectomized animals, they daily received either subcutaneous administration of estrogen (5 µg/0.1 ml oil) or progesterone (2 mg/0.1 ml oil) or dihydrotestosterone (25 mg/0.1 ml oil) for thirteen days, from post-conditioning day to reinstatement session. We found that SD facilitated relapse to METH reward memory, depending on the time interval between SD and METH reinstatement. Furthermore, we found that estrogen and SD showed synergistic effects to facilitate METH reward memory, whereas testosterone and progesterone revealed inhibitory effects in the controls, but not in the SD, animals. Our findings would seem to suggest that sex hormones should be considered as determinant factors to manage METH abuse and relapse to METH seeking/taking behavior, especially for those with sleep deficiency.
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Transtornos Relacionados ao Uso de Anfetaminas , Estimulantes do Sistema Nervoso Central , Metanfetamina , Ratos , Masculino , Feminino , Animais , Metanfetamina/farmacologia , Ratos Wistar , Privação do Sono , Progesterona/farmacologia , Progesterona/uso terapêutico , Condicionamento Operante , Estimulantes do Sistema Nervoso Central/farmacologia , Recompensa , Estrogênios/farmacologia , Estrogênios/uso terapêutico , Recidiva , Extinção PsicológicaRESUMO
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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Canabinoides , Memória , Ratos , Animais , Rimonabanto/farmacologia , Sono REM , Receptores de Canabinoides , Canabinoides/farmacologiaRESUMO
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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BACKGROUND: Suicidal behavior is a major mental health concern both for the individual and for the public health. Among others, suicidal behavior is associated with impulsivity, risk taking, pain tolerance, and a state of overarousal. In the present study, we investigated if suicide attempters (SAs) reported higher scores for risk-taking when compared with healthy controls (HC) of the general population. METHODS: A total of 616 individuals (mean age: 27.07 years; 51.5% females) took part in the study; of those, 240 (39%) were individuals with a suicide attempt (SA) within a time lapse of one to three months, and 376 (61%) were healthy controls (HC). Participants completed a series of self-rating questionnaires covering sociodemographic information, risk-taking (Risk-Taking Questionnaire 18; RT-18), and suicidal behavior (Suicide Behaviors Questionnaire-Revised; SBQ-R). RESULTS: Compared with HCs, individuals with SA reported higher risk-taking and suicidal behavior scores. The risk-taking questionnaire yielded a four-factor solution: Thrill and sensation seeking; Cautious procedure; Cautious decision making; Impulsive behavior. Compared with HCs, SAs showed the highest scores for thrill and sensation seeking and impulsive behavior. CONCLUSIONS: Compared with healthy controls, individuals reporting a recent suicide attempt also reported a higher propensity to thrill and sensation seeking and impulsive behavior as a proxy of risk-taking behavior. The present results corroborate the notion that, among others, suicide attempts appeared to be less related to premeditation, but rather to impulsive and thus spontaneous behavior.
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Maternal sleep-deprivation (MSD) has been shown to induce stress, hyperactivity, and risk taking behavior in the offspring; howbeit, it is not yet clear whether it may also affect vulnerability to psychostimulant abuse in the offspring. We aimed to determine whether MSD affects extinction and reinstatement of methamphetamine (METH) reward memory in the offspring and also to evaluate the possible role of dopamine D1-like and D2-like receptors in these processes. Thirty-day-old male offspring born to control and sleep-deprived dams (during the third week of pregnancy) were trained to acquire METH-induced place preference (2 mg/kg., i.p.). METH reward memory was then reinstated following an 8-day period of extinction. The offspring received SCH 23390 (0.03 or 0.1 mg/kg, i.p.) or sulpiride (20 or 60 mg/kg, i.p.) as antagonists of dopamine D1-like and D2-like receptors, respectively, either immediately after each daily extinction session or prior to the reinstatement session. MSD postponed METH extinction and facilitated METH reinstatement in the offspring. SCH 23390 facilitated METH extinction and decreased reinstatement of the extinguished METH preference. Sulpiride in the offspring from sleep-deprived dams facilitated METH extinction, but it did not affect reinstatement of the extinguished METH reward memory. It seems that MSD may enhance vulnerability to METH abuse in the offspring. Furthermore, both dopamine D1-like and D2-like receptors may mediate METH extinction in the offspring born to the sleep-deprived dams; however, only the dopamine D1 receptor may play an important role in reinstating the extinguished METH reward memory in the offspring.
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Metanfetamina , Animais , Dopamina , Extinção Psicológica , Masculino , Metanfetamina/farmacologia , Morfina/farmacologia , Ratos , Ratos Wistar , Receptores de Dopamina D1 , Receptores de Dopamina D2 , Recompensa , Privação do Sono , Sulpirida/farmacologiaRESUMO
This study set out to assess restingstate functional connectivity (rs-FN) and graph theorybased local efficiency within the left and right hemispheres of methamphetamine (MA) users. Functional brain networks of 19 MA users and 21 control participants were analyzed using restingstate fMRI. Graph edges in functional networks of the brain were defined and recurrence plot was used. We found that MA abuse may be accompanied by alterations of rs-FN within the defaultmode network (DMN), executive control network (ECN), and the salience network (SN) in both hemispheres of the brain. Moreover, we observed that such effects of MA may be correlated with duration of MA abuse and MA abstinence in many components of the DMN and SN. The results would seem to suggest that MAinduced alterations of local efficiency may, in part, account for maladaptive decision making, deficits in executive function and control over drug seeking/taking, and relapse.
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Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Encéfalo , Mapeamento Encefálico , Humanos , Imageamento por Ressonância MagnéticaRESUMO
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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Canabinoides , Metanfetamina , Síndromes Neurotóxicas , Animais , Antagonistas de Receptores de Canabinoides/farmacologia , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/prevenção & controle , Metanfetamina/toxicidade , Ratos , Receptor CB1 de Canabinoide , RimonabantoRESUMO
Motor and psychiatric symptoms in patients with Parkinson's disease (PD) constitute some of the most problematic issues for both the patients and their caregivers. This study evaluated the short- and long-term efficacy of electroconvulsive therapy (ECT) in PD patients whose psychiatric symptoms had been exacerbated due to drug therapy. Fifteen PD patients were treated using an electroshock device at a range of 25-100 Joules over a period of 6 weeks, during 12 sessions. Motor and psychiatric symptoms of all patients were evaluated before conducting ECT as baseline, after 12 sessions of ECT at the 6th week, and one month after completion of the treatment at the 10th week. The results showed that the variables mentation, behavior, mood, performance of daily activities, and severity of motor and psychiatric symptoms, were significantly improved at the end of the 6th and 10th weeks when compared with the baseline. Moreover, the results revealed that the mean values were significantly different only for motor symptoms at the end of the study (10th week) compared with the second time point. The current trial may indicate that ECT could potentially serve as a viable treatment for PD patients with refractory psychiatric symptoms. However, due to waning efficacy of ECT, it is recommended that PD patients undergo a conventional treatment in conjunction with periodic ECT sessions to ensure an optimal medical outcome.
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Eletroconvulsoterapia/métodos , Doença de Parkinson/terapia , Adulto , Idoso , Eletroconvulsoterapia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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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Comportamento de Procura de Droga/efeitos dos fármacos , Metanfetamina/farmacologia , Transtorno do Comportamento do Sono REM/metabolismo , Receptores de Dopamina D1/metabolismo , Privação do Sono/metabolismo , Animais , Benzazepinas/farmacologia , Condicionamento Psicológico/efeitos dos fármacos , Dopaminérgicos/farmacologia , Extinção Psicológica/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de Dopamina D2/metabolismo , Recompensa , Sono REM , Sulpirida/farmacologiaRESUMO
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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Ansiedade/metabolismo , Encéfalo/metabolismo , Estrogênios/uso terapêutico , Metanfetamina/toxicidade , Ovariectomia/efeitos adversos , Progesterona/uso terapêutico , Animais , Ansiedade/induzido quimicamente , Ansiedade/prevenção & controle , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Estimulantes do Sistema Nervoso Central/toxicidade , Estrogênios/farmacologia , Feminino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Ovário/metabolismo , Progesterona/farmacologia , Ratos , Ratos WistarRESUMO
INTRODUCTION: Cyclic nucleotide phosphodiesterase (PDE) enzymes are a large superfamily of enzymes that catalyze the conversion reaction of cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) to AMP and GMP, respectively. In some cancer cells, PDE-5 has been shown to be overexpressed in multiple human carcinomas. It seems that the inhibition of PDE-5 may has anticancer effects. Cisplatin is one of the prevalent chemo-agents to treat solid tumors. However, its clinical usefulness is hindered by dose-limiting toxicities, especially on the kidneys (nephrotoxicity) and ears (ototoxicity). In this study, the antitumor activity of the sildenafil as a PDE-5 inhibitor alone and in combination with cisplatin on human mammary adenocarcinomas and MCF-7 and MDA-MB-468 was assessed. MATERIALS AND METHODS: Sildenafil as PDE type 5 (PDE5) inhibitor is the drugs that we combined with the cisplatin (chemotherapeutic agent), in vitro. Human mammary adenocarcinomas and MCF-7 and MDA-MB-468 cell lines were cultured in standard conditions. At time point, following 24 h and 48 h incubation, the cell lines were treated by cisplatin in the presence/absence of sildenafil. Cell viability, apoptosis, and reactive oxygen species (ROS) were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, real-time polymerase chain reaction, and Western blot; and fluorimetric methods, respectively. Statistical analysis was performed using SPSS software SPSS (SPSS Inc., Chicago, IL, USA). RESULTS: In MCF-7 cell line, following 24 h incubation, combinations of sildenafil with cisplatin (P < 0.001) showed decreased cell viability when compared to sildenafil and cisplatin alone. Moreover in MDA-MB-468 cell line, following 24 h incubation, data did not show any significant changes on cell viability when treated with cisplatin, in the presence or absence of sildenafil. However, following 48 h incubation, combinations of cisplatin with sildenafil (P < 0.001) were showed decreased cell viability when compared to cisplatin and sildenafil alone in both MCF-7 and MDA-MB-468 cell lines. Concerning the ROS production and apoptosis, data showed that both processes increase significantly in the presence of the sildenafil in comparison absent it. CONCLUSION: Our data showed that the combination of sildenafil with cisplatin can improve cell toxicity and anticancer effect of cisplatin. And also sildenafil as a PDE-5 inhibitor could be used as additive treatment in combination with cisplatin to make a reduction in cisplatin dosage and its side effects.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cisplatino/farmacologia , Citrato de Sildenafila/farmacologia , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Cisplatino/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Feminino , Humanos , Células MCF-7 , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Citrato de Sildenafila/uso terapêuticoRESUMO
Methamphetamine (MA) and other psychostimulants target the motive circuit of the brain, which is involved in reward, behavioral sensitization, and relapse to drug-seeking/taking behavior. In spite of this fact, the data regarding the effective connectivity (EC) in this circuit among MA users is scarce. The present study aimed to assess resting-state EC in the motive circuit of MA users during abstinence using the fMRI technique. Seventeen MA users after abstinence and 18 normal controls were examined using a 3 T Siemens fMRI scanner. After extracting time series of the motive circuit, EC differences in the motive circuit were analyzed using dynamic causal modeling (DCM). The findings revealed that abstinent MA users had an enhanced EC from the prefrontal cortex (PFC) to the ventral palladium (VP) (PFCâVP) and on the mediodorsal thalamus (MD) self-loop (MDâMD), but they showed a decreased connectivity on the VP self-loop (VPâVP) compared to healthy controls. The findings suggest that abstinent MA users may suffer from a limited pathology in connectivity within the motive circuit involved in reward, behavioral sensitization, and relapse. The enhanced PFCâVP seems to be a compensatory mechanism to control or regulate the subcortical regions involved in reward and behavioral sensitization. Furthermore, the enhanced connectivity on the MD self-loop and the decreased connectivity on the VP self-loop in abstinent MA users may, at least partially, affect the output of the limbic system, which can be seen in the behavioral sensitization and relapse processes. Nonetheless, further investigation in this area is strongly recommended to elucidate the exact mechanisms involved.
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Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico por imagem , Prosencéfalo Basal/diagnóstico por imagem , Núcleo Mediodorsal do Tálamo/diagnóstico por imagem , Metanfetamina , Córtex Pré-Frontal/diagnóstico por imagem , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/fisiopatologia , Prosencéfalo Basal/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Núcleo Mediodorsal do Tálamo/fisiopatologia , Pessoa de Meia-Idade , Motivação , Vias Neurais , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Área Tegmentar Ventral/diagnóstico por imagem , Área Tegmentar Ventral/fisiopatologia , Adulto JovemRESUMO
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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Teste de Campo Aberto/fisiologia , Receptor CB1 de Canabinoide/fisiologia , Reconhecimento Psicológico/fisiologia , Privação do Sono/fisiopatologia , Animais , Antagonistas de Receptores de Canabinoides/farmacologia , Corticosterona/sangue , Teste de Campo Aberto/efeitos dos fármacos , Ratos , Receptor CB1 de Canabinoide/antagonistas & inibidores , Reconhecimento Psicológico/efeitos dos fármacos , Rimonabanto/farmacologia , Estresse Psicológico/sangueRESUMO
Background Modulatory effects of soy extract and estradiol on the central nervous system (CNS) have been reported. The effect of soy on scopolamine-induced spatial learning and memory in comparison to the effect of estradiol was investigated. Materials and methods Ovariectomized rats were divided into the following groups: (1) control, (2) scopolamine (Sco), (3) scopolamine-soy 20 (Sco-S 20), (4) scopolamine-soy 60 (Sco-S 60), (5) scopolamine-estradiol 20 (Sco-E 20) and (6) scopolamine-estradiol 60 (Sco-E 60). Soy extract, estradiol and vehicle were administered daily for 6 weeks before training in the Morris water maze (MWM) test. Scopolamine (2 mg/kg) was injected 30 min before training in the MWM test. Results In the MWM, the escape latency and traveled path to find the platform in the Sco group was prolonged compared to the control group (p < 0.001). Treatment by higher doses of soy improved performances of the rats in the MWM (p < 0.05 - p < 0.001). However, treatment with both doses of estradiol (20 and 60 µg/kg) resulted in a statistically significant improvement in the MWM (p < 0.01 - p < 0.001). Cortical, hippocampal and serum levels of malondialdehyde (MDA), as an index of lipid peroxidation, were increased which was prevented by soy extract and estradiol (p < 0.001). Cortical, hippocampal as well as serum levels of the total thiol, superoxide dismutase (SOD) and catalase (CAT) in Sco group were lower than the control group (p < 0.001) while they were enhanced when the animals were treated by soy extract and estradiol (p < 0.01 - p < 0.001). Conclusions It was observed that both soy extract and estradiol prevented learning and memory impairments induced by scopolamine in ovariectomized rats. These effects can be attributed to their protective effects on oxidative damage of the brain tissue.
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Estradiol/farmacologia , Glycine max/química , Transtornos da Memória/etiologia , Memória/efeitos dos fármacos , Extratos Vegetais/farmacologia , Escopolamina/farmacologia , Aprendizagem Espacial/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Biomarcadores , Catalase/metabolismo , Feminino , Aprendizagem em Labirinto , Transtornos da Memória/tratamento farmacológico , Ovariectomia , Oxidantes/metabolismo , Estresse Oxidativo , Extratos Vegetais/química , Ratos , Superóxido Dismutase/metabolismoRESUMO
Susceptibility to interference can be a result of memory retrieval and reconsolidation. Given the fact that addiction develops through the neural mechanisms of learning and memory, it would not be surprising that a consolidated drug reward memory may also be susceptible to interference following retrieval/reconsolidation. Due to the critical role of sleep in memory consolidation, sleep deprivation (SD) has been shown to impair memory. Therefore, the major objective of this study was to investigate the effect of rapid eye movement (REM) sleep deprivation (RSD) on the retrieval and reconsolidation of methamphetamine (METH) reward memory in male rats. The animals were trained to acquire METH-induced CPP (2â¯mg/kg, i.p.). METH reward memory was then reactivated/retrieved in the drug-paired chamber during a drug-free (memory reactivation) session. A period of 48-h RSD paradigm using the multiple platform technique resulted in persistent deficits in the retrieval of METH reward memory. Nevertheless, the same protocol of RSD, which was conducted immediately after the memory reactivation, did not affect the reconsolidation of METH reward memory. Additionally, the RSD episode induced a temporary potentiation of METH-induced hyperlocomotion. Our findings would seem to suggest that sleep is involved in the retrieval, but not reconsolidation, of METH reward memory. The results may also demonstrate that RSD mimics the effects of METH on locomotor activity. The results of this study, therefore, support the idea that sleep is involved in the processing of METH reward memory which can be considered for further investigations to manage the relapse associated with drug-related memory.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Memória/efeitos dos fármacos , Metanfetamina/farmacologia , Recompensa , Privação do Sono/psicologia , Sono REM/fisiologia , Animais , Comportamento Aditivo , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Comportamento de Procura de Droga , Locomoção/efeitos dos fármacos , Masculino , Metanfetamina/administração & dosagem , Ratos , Ratos Wistar , Recidiva , Solução Salina/administração & dosagem , Solução Salina/farmacologia , Privação do Sono/fisiopatologiaRESUMO
Neonatal administration of MK-801 (NMDA receptor antagonist) results in schizophrenia-like behaviors in rodents. Berberine (BBR) is a herbal alkaloid, which shows many neuroprotective properties in neurodegenerative diseases. The present study was designed to clarify whether systemic administration of BBR improves motor and cognitive disturbances induced by MK-801 treatment. Male Wistar rat pups were treated with intraperitoneal administration of saline (1 ml/kg) as a control group, MK-801 (1 mg/kg), BBR (20 mg/kg) and BBR (20 mg/kg) plus MK- 801 (1 mg/kg). Treatments were administered on postnatal day (P) 6-10 for once daily. To assess motor learning, coordination as well as spatial learning and memory, behavioral evaluation was performed at P55-60, using the rotarod, open field, and Morris water maze paradigm. MK-801 injection led to motor perturbations in both the open field and accelerating rotarod tests, which were restored by BBR. Also, BBR improved learning impairments, although it had no significant effect on the Probe test. Taken together, it can be concluded that BBR produces a neuroprotective effect in rats with MK-801-associated behavioral deficits. Given that the MK-801 exposure demonstrates an animal model of schizophrenia, we suggest that timely BBR administration may act as a potential treatment in schizophrenic patients.
Assuntos
Berberina/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Transtornos Motores/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Esquizofrenia/tratamento farmacológico , Animais , Animais Recém-Nascidos , Berberina/farmacologia , Disfunção Cognitiva/induzido quimicamente , Modelos Animais de Doenças , Maleato de Dizocilpina , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos Motores/induzido quimicamente , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Wistar , Esquizofrenia/induzido quimicamenteRESUMO
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.