RESUMO
The Amazon forest carbon sink is declining, mainly as a result of land-use and climate change1-4. Here we investigate how changes in law enforcement of environmental protection policies may have affected the Amazonian carbon balance between 2010 and 2018 compared with 2019 and 2020, based on atmospheric CO2 vertical profiles5,6, deforestation7 and fire data8, as well as infraction notices related to illegal deforestation9. We estimate that Amazonia carbon emissions increased from a mean of 0.24 ± 0.08 PgC year-1 in 2010-2018 to 0.44 ± 0.10 PgC year-1 in 2019 and 0.52 ± 0.10 PgC year-1 in 2020 (± uncertainty). The observed increases in deforestation were 82% and 77% (94% accuracy) and burned area were 14% and 42% in 2019 and 2020 compared with the 2010-2018 mean, respectively. We find that the numbers of notifications of infractions against flora decreased by 30% and 54% and fines paid by 74% and 89% in 2019 and 2020, respectively. Carbon losses during 2019-2020 were comparable with those of the record warm El Niño (2015-2016) without an extreme drought event. Statistical tests show that the observed differences between the 2010-2018 mean and 2019-2020 are unlikely to have arisen by chance. The changes in the carbon budget of Amazonia during 2019-2020 were mainly because of western Amazonia becoming a carbon source. Our results indicate that a decline in law enforcement led to increases in deforestation, biomass burning and forest degradation, which increased carbon emissions and enhanced drying and warming of the Amazon forests.
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Dióxido de Carbono , Sequestro de Carbono , Conservação dos Recursos Naturais , Política Ambiental , Aplicação da Lei , Floresta Úmida , Biomassa , Brasil , Dióxido de Carbono/análise , Dióxido de Carbono/metabolismo , Política Ambiental/legislação & jurisprudência , Atmosfera/química , Incêndios Florestais/estatística & dados numéricos , Conservação dos Recursos Naturais/estatística & dados numéricos , El Niño Oscilação Sul , Secas/estatística & dados numéricosRESUMO
Multivariate calibration based on partial least squares, random forest, and support vector machine methods, combined with the MissForest imputation algorithm, was used to understand the interaction between ozone and nitrogen oxides, carbon monoxide, wind speed, solar radiation, temperature, relative humidity, and others, the data of which were collected by air quality monitoring stations in the metropolitan area of Rio de Janeiro in four distinct sites between, 2014 and, 2018. These techniques provide an easy and feasible way of modeling and analyzing air pollutants and can be used when coupled with other methods. The results showed that random forest and support vector machine chemometric techniques can be used in modeling and predicting tropospheric ozone concentrations, with a coefficient of determination for making predictions up to 0.92, a root-mean square error of calibration between 4.66 and 27.15 µg m-3, and a root-mean square error of prediction between 4.17 and 22.45 µg m-3, depending on the air quality monitoring stations and season.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Brasil , Calibragem , Monitoramento Ambiental , Ozônio/análiseRESUMO
Methylphenidate (MET) has a putative cognitive enhancer effect that has led adolescents and young adults to increase and indiscriminate its use aiming to ameliorate their productivity. However, the impacts of MET on addiction-related behaviors, emotional levels, and cognition are still not fully understood. To investigate the influence of chronic treatment with MET during adolescence on addiction-like behaviors, memory, and anxiety in adult mice. Thirty-day-old female mice received i.p. 10 mg/kg MET or Veh injections for 10 consecutive days. Forty days after the treatment (mice were 70-days-old), animals were submitted to the behavioral evaluation under the effects of MET, which included: MET-induced conditioned place preference (CPP), behavioral sensitization, and plus-maze discriminative avoidance task. Pre-exposure to MET during adolescence promoted an early expression of CPP and also facilitated the development of MET-induced behavioral sensitization during adulthood. These addictive-like behaviors were accompanied by anxiogenic effects of MET but not by any memory-enhancing effect. We demonstrated that exposure to MET during adolescence can increase the vulnerability to addiction-like behaviors and anxiety during adulthood. Our results reinforce the necessity of a more efficient system to control MET indiscriminate use, thus avoiding its potential tardive addictive effects.
Assuntos
Ansiedade/metabolismo , Comportamento Aditivo/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Memória/efeitos dos fármacos , Metilfenidato/farmacologia , Animais , Ansiedade/psicologia , Comportamento Aditivo/psicologia , Comportamento Animal/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Feminino , Humanos , Camundongos , Modelos Animais , Atividade Motora/efeitos dos fármacosRESUMO
BACKGROUND Mixed adenoneuroendocrine carcinoma of the gallbladder (gMANEC) is an extremely rare cancer. Most of the cases are reported in Asia, North America, and Europe, with no cases reported in Latin America; this is the first report for this region, and the 24th case reported worldwide. CASE REPORT A 68-year-old woman was referred to our department due to asthenia and moderate abdominal pain in the right upper quadrant for 6 months, with imaging examinations showing a solid heterogeneous expansive lesion in gallbladder topography and segment IV of the liver. The MRI displayed an expansive and heterogeneous lesion with inaccurate limits in the gallbladder affecting segment IVb of the liver, in addition to lymphadenopathy in the hepatic hilum. A cholecystectomy with resection of segments IV-B and V of the liver (radical cholecystectomy) and hepatic hilar lymphadenectomy were performed. Anatomopathological examination and immunohistochemistry confirmed a primary mixed adenoneuroendocrine carcinoma of the gallbladder. The patient received adjuvant chemotherapy and radiotherapy; however, after the patient reported experiencing low back pain, a CT was performed, revealing retroperitoneal metastasis, and the radiotherapy was interrupted. Currently, the patient has a stable disease, following a protocol of 5-Fluorouracil and somatostatin, and she reports having low back pain of low intensity. CONCLUSIONS This is the 24th gMANEC case reported in the literature. The tumor was successfully resected; however, the patient presented retroperitoneal metastasis 6 months after surgery, despite combined adjuvant therapy.
Assuntos
Adenocarcinoma , Neoplasias da Vesícula Biliar , Idoso , Colecistectomia , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Excisão de LinfonodoRESUMO
BACKGROUND: Prenatal environmental adversities may affect brain development and are associated with increased risk for schizophrenia, an illness with 50% comorbidity with addiction. Maternal immune activation by poly-inosinic-citidilic acid (Poly(I:C)) exposure can promote behavioral alterations consistent with schizophrenia symptoms in rodents. OBJECTIVES: Considering the vulnerability to addiction in patients with schizophrenia, we evaluated the interactions between prenatal Poly(I:C) administration and addiction in two animal models (behavioral sensitization and conditioned place preference - CPP) in mice repeatedly treated with amphetamine (AMP). Additionally, stereotyped behavior and cross-sensitization with cocaine (COC) were also investigated. METHODS: Swiss male mice offspring were submitted to prenatal administration of 5mg/kg Poly(I:C) in the 9(th) day of pregnancy. At the age of 90days, mice were treated with 2.5mg/kg AMP for 9days to evaluate behavioral sensitization or stereotyped behavior. Cross-sensitization with 10mg/kg COC was evaluated 24h after the last treatment day. For AMP-induced CPP evaluation, mice were treated during 8 consecutive days. RESULTS: Prenatal Poly(I:C) administration potentiated both AMP-induced behavioral sensitization and CPP. Furthermore, Poly(I:C) increased cross-sensitization with COC. CONCLUSIONS: Prenatal administration of Poly(I:C) is able to potentiate vulnerability to addiction in two animal models, without however modulating stereotyped behavior.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/etiologia , Transtornos Relacionados ao Uso de Anfetaminas/imunologia , Comportamento Exploratório/fisiologia , Poli I-C/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Cocaína/toxicidade , Condicionamento Psicológico/fisiologia , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Feminino , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Gravidez , Comportamento Estereotipado/fisiologia , Fatores de TempoRESUMO
To examine how community-level genetic diversity of the malaria parasite Plasmodium vivax varies across time and space, we investigated the dynamics of parasite polymorphisms during the early phases of occupation of a frontier settlement in the Amazon Basin of Brazil. Microsatellite characterization of 84 isolates of P. vivax sampled over 3 years revealed a moderate-to-high genetic diversity (mean expected heterozygosity, 0.699), with a large proportion (78.5%) of multiple-clone infections (MCI), but also a strong multilocus linkage disequilibrium (LD) consistent with rare outcrossing. Little temporal and no spatial clustering was observed in the distribution of parasite haplotypes. A single microsatellite haplotype was shared by 3 parasites collected during an outbreak; all other 81 haplotypes were recovered only once. The lowest parasite diversity, with the smallest proportion of MCI and the strongest LD, was observed at the time of the outbreak, providing a clear example of epidemic population structure in a human pathogen. Population genetic parameters returned to pre-outbreak values during last 2 years of study, despite the concomitant decline in malaria incidence. We suggest that parasite genotyping can be useful for tracking the spread of new parasite strains associated with outbreaks in areas approaching malaria elimination.
Assuntos
Variação Genética , Malária Vivax/parasitologia , Plasmodium vivax/genética , Brasil/epidemiologia , Estudos de Coortes , Haplótipos , Humanos , Incidência , Malária Vivax/epidemiologia , Repetições de Microssatélites , Plasmodium vivax/fisiologia , População Rural , Fatores de TempoRESUMO
BACKGROUND: New frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings. METHODS: Eight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease. PRINCIPAL FINDINGS/CONCLUSIONS: P. vivax prevalence decreased from 23.8% (March-April 2010) to 3.0% (April-May 2013), with no P. falciparum infections diagnosed after March-April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2-3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance.
Assuntos
Malária Vivax/epidemiologia , Plasmodium vivax/genética , Adulto , Brasil/epidemiologia , Feminino , Humanos , Malária Vivax/parasitologia , Malária Vivax/transmissão , Masculino , Parasitemia/epidemiologia , Parasitemia/parasitologia , Reação em Cadeia da Polimerase , População Rural/estatística & dados numéricos , Adulto JovemRESUMO
The prospective cross-sectional study investigated the 6MWT performance in pediatric group of liver transplant recipients (6-17 yr, median post-transplantation time of 22 months) and compared to the normal values obtained in healthy children as well as evaluated the reproducibility of the 6MWT. We analyzed the relationship between walked distance and the 6MWw, distance walked × body weight) with the anthropometric, clinical, and pulmonary functions. In post-transplanted group, the average walked distance was significantly shorter compared with control (687 ± 80 m vs. 511 ± 72 m, p < 0.001). The calculated ICC coefficient confirmed the reproducibility among tests. The Pearson correlation revealed that only walked distance in the 6MWT was moderately correlated with tidal volume. Conversely, the 6MWw was significantly correlated with age, weight, height, BMI, FVC, PEF rate, and volume expiratory. According to multiple regression analysis, age, VE and FVC factors explained 80% of the variance in the 6MWw. In conclusion, the pediatric liver transplant recipients' performance in the 6MWT is significantly lower than the values for healthy children of the same age. Notably, the 6MWw may provide relevant information, constituting an additional parameter in the determination of functional capacity.
Assuntos
Transplante de Fígado , Aptidão Física , Caminhada/fisiologia , Adolescente , Antropometria , Brasil , Criança , Estudos Transversais , Teste de Esforço , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Reprodutibilidade dos Testes , Testes de Função RespiratóriaRESUMO
PURPOSE: Mucopolysaccharidosis (MPS) encompasses a group of rare lysosomal storage disorders that are associated with the accumulation of glycosaminoglycans in organs and tissues. Respiratory disorders occur in all MPS types. In these patients, the prevalence of obstructive sleep apnea syndrome (OSAS), which may confer additional morbidity, remains overlooked, and the results of the few existing studies are controversial. The present study aimed to characterize the prevalence of OSAS in patients with MPS types I, II, and VI in a reference center. METHODS: Forty-five patients with MPS (I, n=17; II, n=16; and VI; n=12) in the Centro de Referência em Erros Inatos do Metabolismo, who underwent full-night polysomnography, were enrolled in a retrospective study. Demographic data and clinical history were collected from medical records of the first medical consultation. RESULTS: The prevalence of OSAS in patients with MPS was 69.8%. MPS type I patients seemed to be more susceptible to OSA-induced hypoxemia, as indicated by reduced mean SpO2 levels during both NREM and rapid eye movement sleep as well as during SpO2 nadir. CONCLUSIONS: Patients with MPS displayed a high prevalence of OSAS, often with moderate to high severity. Together, our results reinforce the need for OSAS screening in all patients with MPS.
Assuntos
Mucopolissacaridose II/epidemiologia , Mucopolissacaridose I/epidemiologia , Mucopolissacaridose VI/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Adolescente , Brasil , Criança , Pré-Escolar , Comorbidade , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Mucopolissacaridose I/diagnóstico , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose VI/diagnóstico , Polissonografia , Estudos Retrospectivos , Apneia Obstrutiva do Sono/diagnóstico , Adulto JovemRESUMO
Alzheimer's disease (AD) is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits, such as alterations in social interactions. The major pathological features of AD are the formation of senile plaques and neurofibrillary tangles together with neuronal and vascular damage. The double transgenic mouse model of AD (2xTg-AD) with the APPswe/PS1dE9 mutations shows characteristics that are similar to those observed in AD patients, including social memory impairment, senile plaque formation and vascular deficits. Mesenchymal stem cells (MSCs), when transplanted into the brain, produce positive effects by reducing amyloid-beta (Aß) deposition in transgenic amyloid precursor protein (APP)/presenilins1 (PS1) mice. Vascular endothelial growth factor (VEGF), exhibits neuroprotective effects against the excitotoxicity implicated in the AD neurodegeneration. The present study investigates the effects of MSCs overexpressing VEGF in hippocampal neovascularization, cognitive dysfunction and senile plaques present in 2xTg-AD transgenic mice. MSC were transfected with vascular endothelial growth factor cloned in uP vector under control of modified CMV promoter (uP-VEGF) vector, by electroporation and expanded at the 14th passage. 2xTg-AD animals at 6, 9 and 12 months old were transplanted with MSC-VEGF or MSC. The animals were tested for behavioral tasks to access locomotion, novelty exploration, learning and memory, and their brains were analyzed by immunohistochemistry (IHC) for vascularization and Aß plaques. MSC-VEGF treatment favored the neovascularization and diminished senile plaques in hippocampal specific layers. Consequently, the treatment was able to provide behavioral benefits and reduce cognitive deficits by recovering the innate interest to novelty and counteracting memory deficits present in these AD transgenic animals. Therefore, this study has important therapeutic implications for the vascular damage in the neurodegeneration promoted by AD.
RESUMO
1. It has been suggested that the high prevalence of drug abuse in schizophrenics is related to chronic treatment with typical neuroleptics and dopaminergic supersensitivity that develops as a consequence. Within this context, atypical neuroleptics do not seem to induce this phenomenon. In the present study, we investigated the effects of acute administration or withdrawal from long-term administration of haloperidol and/or ziprasidone on morphine-induced open-field behaviour in mice. 2. In the first experiment, mice were given a single injection of haloperidol (1 mg/kg, i.p.) or several doses of ziprasidone (2, 4 or 6 mg/kg, i.p.) and motor activity was quantified by the open-field test. The aim of the second experiment was to verify the effects of an acute injection of haloperidol (1 mg/kg) or ziprasidone (6 mg/kg) on 20 mg/kg morphine-induced behaviours in the open-field test. In the third experiment, mice were treated with 1 mg/kg haloperidol and/or 2, 4 or 6 mg/kg ziprasidone for 20 days. Seventy-two hours after the last injection, mice were injected with 20 mg/kg, i.p., morphine and then subjected to the open-field test. Acute haloperidol or ziprasidone decreased spontaneous general activity and abolished morphine-induced locomotor stimulation. 3. Withdrawal from haloperidol or ziprasidone did not modify morphine-elicited behaviours in the open-field test. The results suggest that withdrawal from neuroleptic treatments does not contribute to the acute effect of morphine in schizophrenic patients.
Assuntos
Antipsicóticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Morfina/farmacologia , Animais , Feminino , Haloperidol/farmacologia , Camundongos , Atividade Motora/efeitos dos fármacos , Piperazinas/farmacologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Tiazóis/farmacologiaRESUMO
We investigated whether the effect of neonatal hypoxia on amphetamine-induced hyperlocomotion can reproduce the ontogenic (age of onset) properties of schizophrenia. Neonatal hypoxia enhanced amphetamine-induced hyperlocomotion in adult mice and decreased it in adolescent mice. These findings provide ontogenic validity for this very simple animal model of schizophrenia.
Assuntos
Dextroanfetamina/farmacologia , Hipercinese/induzido quimicamente , Hipóxia/psicologia , Esquizofrenia/induzido quimicamente , Fatores Etários , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Masculino , CamundongosRESUMO
While the effects of sleep deprivation (SD) on the acquisition and consolidation phases of memory have been extensively characterized, its effects on memory retrieval remain overlooked. SD alone is a stressor, and stress-activated glucocorticoids promote bimodal effects on memory. Because we have recently demonstrated that 72h SD impairs memory retrieval in the plus-maze discriminative avoidance task (PM-DAT) in mice, this study investigated whether shorter SD periods would facilitate retrieval. In Experiment I, the temporal forgetting curve of the PM-DAT was determined and an interval between training/testing in which retrieval was no longer present was used in all subsequent experiments. In Experiments II and III, retrieval performance and corticosterone concentration, respectively, were quantified in mice that were sleep deprived for 12 or 24h before testing. In Experiments IV and V, the effects of the corticosterone synthesis inhibitor metyrapone were evaluated on 12h SD-induced retrieval reinstatement and corticosterone concentration enhancement, respectively. Experiment VI determined whether pre-test acute administration of exogenous corticosterone would mimic the facilitatory effects of 12h SD on retrieval. Thirty days after training, mice presented poor performance of the task; however, SD for 12h (but not for 24) before testing reinstated memory retrieval. This facilitatory effect was accompanied by increased corticosterone concentration, abolished by metyrapone, and mimicked by pre-test acute corticosterone administration. Collectively, short-term SD can facilitate memory retrieval by enhancing corticosterone secretion. This facilitatory effect is abolished by longer periods of SD.
Assuntos
Corticosterona/fisiologia , Rememoração Mental/fisiologia , Privação do Sono/psicologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Corticosterona/metabolismo , Corticosterona/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Memória/fisiologia , Rememoração Mental/efeitos dos fármacos , Metirapona/farmacologia , Camundongos , Privação do Sono/sangue , Privação do Sono/fisiopatologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Fatores de TempoRESUMO
OBJECTIVES: Sleep deprivation is a growing public health hazard, yet it is still under-recognized. Sleep disorders and disruption of sleep patterns may compromise the immune function and adversely affect host resistance to infectious diseases. This is a particular risk in cancer patients, who report a high frequency of sleep disturbances. The present study investigated the effects of sleep deprivation on the development of Ehrlich ascitic tumors (EAT) in female BALB/c mice. Our study also evaluated whether EAT would induce alterations in sleep pattern. Spleen lymphocyte cell populations and mortality were also quantified. METHODS: Female BALB/c mice were intraperitoneally inoculated with EAT cells. Immediately after the inoculation procedure, animals were sleep deprived for 72 h. Ten or 15 days after inoculation, the number of tumoral cells was quantified and the lymphocytic cell population in the spleen was characterized by flow cytometry. In addition, the effect of sleep deprivation on EAT-induced mortality was quantified and the influence of EAT on sleep patterns was determined. RESULTS: Sleep deprivation did not potentiate EAT growth, but it significantly increased mortality. Additionally, both EAT and sleep deprivation decreased frequencies of splenic CD4+, CD8+ and CD19+ cells. With respect to sleep patterns, EAT significantly enhanced paradoxical sleep time. CONCLUSIONS: Although sleep deprivation did not potentiate EAT growth, it decreased the survival of female tumor-bearing mice.
Assuntos
Carcinoma de Ehrlich/mortalidade , Privação do Sono/complicações , Análise de Variância , Animais , Antígenos CD/metabolismo , Carcinoma de Ehrlich/imunologia , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Humanos , Linfócitos/imunologia , Linfócitos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias/métodos , Baço/patologiaRESUMO
Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine before training and/or before testing both in the plus-maze discriminative avoidance task (an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity) and in the inhibitory avoidance task, a classic paradigm for evaluating memory in rodents. Pre-training caffeine administration did not modify learning, but produced an anxiogenic effect and impaired memory retention. While pre-test administration of caffeine did not modify retrieval on its own, the pre-test administration counteracted the memory deficit induced by the pre-training caffeine injection in both the plus-maze discriminative and inhibitory avoidance tasks. Our data demonstrate that caffeine-induced memory deficits are critically related to state-dependent learning, reinforcing the importance of considering the participation of state-dependency on the interpretation of the cognitive effects of caffeine. The possible participation of caffeine-induced anxiety alterations in state-dependent memory deficits is discussed.
Assuntos
Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Inibição Psicológica , Aprendizagem/efeitos dos fármacos , Análise de Variância , Animais , Masculino , Transtornos da Memória/induzido quimicamente , CamundongosRESUMO
BACKGROUND: A considerable amount of experimental evidence has demonstrated ethanol (EtOH) induced amnestic effects following EtOH administration during pretraining in a variety of tasks both in humans and in laboratory animals. Although the phenomenon of state-dependency is known to play a critical role in memory deficits induced by both pharmacological and nonpharmacological pretraining perturbations, the involvement of this phenomenon in EtOH-induced anterograde amnesia has been overlooked. This study aimed to investigate the role of state-dependency in EtOH-induced amnestic effects and its interactions with the well-known anxiolysis and locomotor alterations. METHODS: Mice were treated with 1.2 or 2.4 g/kg EtOH before training and/or before testing in the plus-maze discriminative avoidance task, an animal model that concomitantly evaluates learning, memory, anxiety-like behavior, and general activity. RESULTS: Whereas both doses of EtOH induced anxiolysis, the 1.2 g/kg dose enhanced locomotion while the 2.4 g/kg dose decreased it. In addition, the administration of 1.2 g/kg of this drug during pretraining caused memory impairment, which was counteracted by the pretest administration of the same dose, revealing the participation of the state-dependency. Conversely, the administration of 2.4 g/kg EtOH led to amnestic effects irrespective of the time of the administration (pretraining and/or pretest), eliminating the influence of state-dependency. CONCLUSIONS: Our data demonstrate that EtOH-induced memory deficits are critically related to state-dependency, which can also be affected by the dose range. These results indicate the possible participation of EtOH-induced modifications in anxiety and motor activity levels in relation to state-dependent memory deficits.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem por Discriminação/efeitos dos fármacos , Etanol/toxicidade , Transtornos da Memória/induzido quimicamente , Animais , Aprendizagem da Esquiva/fisiologia , Aprendizagem por Discriminação/fisiologia , Relação Dose-Resposta a Droga , Masculino , Transtornos da Memória/fisiopatologia , Camundongos , Distribuição AleatóriaRESUMO
Modafinil (MOD), a psychostimulant used to treat narcolepsy, excessive daytime sleepiness, and sleepiness due to obstructive sleep apnea, appears to promote a possible facilitatory effect on cognitive function. In the present study, we investigated the effects of the acute administration of MOD on the different steps of emotional memory formation and usage (acquisition, consolidation and retrieval) as well as the possible participation of the state-dependency phenomenon on the cognitive effects of this compound. Mice were acutely treated with 32, 64 or 128 mg/kg MOD before training or testing or immediately after training and were subjected to the plus-maze discriminative avoidance task. The results showed that although pre-training MOD administration did not exert any effects on learning, the doses of 32 or 64 mg/kg induced emotional memory deficits during testing. Still, the post-training acute administration of the higher doses of MOD (64 and 128 mg/kg) impaired associative memory consolidation. When the drug was administered pre-test, only the 32 mg/kg dose impaired the task retrieval. Importantly, the cognitive impairing effects induced by 32 mg/kg MOD were not related to the phenomenon of state-dependency. In all, our findings provide pre-clinical evidence of potential emotional memory amnesia induced by MOD. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
Assuntos
Amnésia/induzido quimicamente , Compostos Benzidrílicos/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Modelos Animais de Doenças , Memória/efeitos dos fármacos , Nootrópicos/efeitos adversos , Substâncias para Melhoria do Desempenho/efeitos adversos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/farmacologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/farmacologia , Transtornos Cognitivos/induzido quimicamente , Aprendizagem por Discriminação/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória Episódica , Camundongos , Modafinila , Nootrópicos/administração & dosagem , Nootrópicos/farmacologia , Substâncias para Melhoria do Desempenho/administração & dosagem , Substâncias para Melhoria do Desempenho/farmacologia , Distribuição Aleatória , Retenção Psicológica/efeitos dos fármacosRESUMO
Previous studies have demonstrated that stress or glucocorticoids impair the retrieval of spatial memory in rodents and declarative memory in humans. However, the effects on memory retrieval of stress introduced a long time after learning have not been well studied. We investigated whether a mild, extrinsic stressor (1-s 0.1 or 0.3 mA foot shock) would reactivate low baseline retrieval of an aversive memory [the plus-maze discriminative avoidance task (PM-DAT)] and if it would be modulated by glucocorticoids. In Experiment 1, male Swiss mice received pre-test foot shock (n = 10 mice/group) 7 days after training and just before testing. A time-retrieval curve for low baseline retrieval for the subsequent experiments was also determined (Experiment 2, n = 10 mice/group). We investigated if pre-test foot shock could modify corticosterone release (Experiment 3, n = 8-9 mice/group) and reinstate retrieval in the PM-DAT (Experiment 4, n = 15 mice/group). The effects of metyrapone (100 mg/kg) on retrieval reinstatement (Experiment 5, n = 15 mice/group) and serum corticosterone enhancement (Experiments 6, n = 7-9 mice/group) induced by foot shock were analyzed. Finally, the effects of foot shock itself on PM-DAT exploration were verified (Experiment 7, n = 10 mice/group). We demonstrated here that foot shock reinstated the retrieval of a low baseline, discriminative avoidance task 30 (but not 7) days after training. This facilitative effect was not dependent on corticosterone secretion because metyrapone abolished the enhancement of corticosterone concentration but did not reverse the stress-induced reinstatement of retrieval.
Assuntos
Aprendizagem da Esquiva , Comportamento Animal , Aprendizagem por Discriminação , Aprendizagem em Labirinto , Rememoração Mental , Estresse Psicológico/psicologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Corticosterona/sangue , Aprendizagem por Discriminação/efeitos dos fármacos , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Camundongos , Piridinas/farmacologia , Esteroide 11-beta-Hidroxilase/antagonistas & inibidores , Esteroide 11-beta-Hidroxilase/metabolismo , Estresse Psicológico/sangue , Fatores de TempoRESUMO
BACKGROUND: Although mood-congruent memory (MCM), or the tendency to recall information consistent with one's mood, is a robust phenomenon in human depression, to our knowledge, it has never been demonstrated in animals. METHODS: Mice were subjected to social isolation (SI) or crowding for 12 hours and had their depressive-like behaviour (evaluated by the forced swim, tail suspension, sucrose preference and splash tests) or their serum corticosterone concentrations evaluated. In addition, we determined the temporal forgetting curve of the plus-maze discriminative avoidance task (PM-DAT) and examined the effects of SI or crowding on memory retrieval in the PM-DAT. Finally, we verified the effects of metyrapone pretreatment on reinstatement of memory retrieval or on the increase of corticosterone levels induced by SI. RESULTS: Twelve hours of SI produced depressive-like behaviour, enhanced corticosterone concentration and reinstated retrieval of a forgotten discriminative aversive (i.e., negatively valenced) task. Depressive-like behaviour was critical for this facilitative effect of SI because 12 hours of crowding neither induced depressive-like behaviour nor enhanced retrieval, although it increased corticosterone levels at the same magnitude as SI. However, corticosterone increase was a necessary condition for MCM in mice, in that the corticosterone synthesis inhibitor metyrapone abolished SI-induced retrieval reinstatement. LIMITATIONS: Our study did not investigate the effects of the social manipulations proposed here in a positively valenced task. CONCLUSION: To our knowledge, the present paper provides the first evidence of MCM in animal models.
Assuntos
Afeto , Aprendizagem da Esquiva/efeitos dos fármacos , Depressão/psicologia , Rememoração Mental/efeitos dos fármacos , Isolamento Social/psicologia , Animais , Comportamento Animal/efeitos dos fármacos , Corticosterona/sangue , Aglomeração/psicologia , Depressão/sangue , Discriminação Psicológica , Masculino , Metirapona/farmacologia , Camundongos , Modelos AnimaisRESUMO
In both humans and laboratory animals, the reports of cognitive effects following acute amphetamine (Amph) administration are mixed and depend, for example, on the timing of administration (e.g. before or after task acquisition) and/or on the memory model used. Besides its cognitive effects, Amph produces other important behavioural effects, including alterations in anxiety and general activity, which could modify the subject's internal state, thereby facilitating state-dependent learning. Importantly, state-dependency has been linked to drug dependence in humans. This study evaluates the role of state-dependent learning in Amph-induced memory deficits in mice submitted to a discriminative avoidance task. Mice were given Amph (3 mg/kg) before training and/or before testing in the plus-maze discriminative avoidance task, an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity. Pre-training Amph administration did not affect the ability to learn the discriminative task, but rather induced anxiogenic-like effects and a marked retention deficit in the test session. This memory impairment was completely absent when animals received Amph before both the training and the test sessions. Amph-induced memory impairment of a discriminative avoidance task is state-dependent, such that a response acquired in the 'Amph state' cannot be recalled in the normal state. The involvement of anxiety alterations in this 'Amph state' is discussed.