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1.
Fa Yi Xue Za Zhi ; 35(5): 576-580, 2019 Oct.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31833292

RESUMO

Abstract: Objective To explore the change rules of blood ethanol and blood acetaldehyde concentration, the impairment of psychomotor functions of different acetaldehyde dehydrogenase (ALDH) 2 genotype individuals after alcohol consumption and the relationship among them. Methods The ALDH2 genotypes in seventy-nine healthy volunteers were obtained by SNaPshotTM method, then divided into ALDH2*1/*1 (wild type) and ALDH2*1/*2 (mutant type) group. After volunteers consumed 1.0 g/kg of alcohol, blood ethanol concentration and blood acetaldehyde concentration at a series of time points before and after alcohol consumption and psychomotor functions, such as, visual selective response time, auditory simple response time and tracking experiment were detected. Biphasic alcohol response questionnaires were collected. Results After alcohol consumption, ALDH2*1/*2 group's blood ethanol and blood acetaldehyde concentration reached the peak earlier than ALDH2*1/*1 group. Its blood acetaldehyde concentration was higher than that of ALDH2*1/*1 group, 1-6 h after alcohol consumption. The psychomotor functions, such as visual selective response time and auditory simple response time in ALDH2*1/*2 group were more significantly impaired than those in ALDH2*1/*1 group after alcohol consumption. There was no statistical significance between the two groups in excitement or sedation reactions (P>0.05). Pearson correlation coefficient test showed that blood acetaldehyde concentration was related with psychomotor function. Conclusion There are significant differences between the psychomotor function of ALDH2 wild type and mutant type individuals after alcohol consumption estimated to be related to the difference in blood acetaldehyde concentration after alcohol consumption.


Assuntos
Acetaldeído/sangue , Consumo de Bebidas Alcoólicas , Aldeído Desidrogenase/genética , Etanol/metabolismo , Polimorfismo Genético/genética , Desempenho Psicomotor/efeitos dos fármacos , Acetaldeído/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Aldeído-Desidrogenase Mitocondrial , Aldeído Oxirredutases , Etanol/administração & dosagem , Etanol/sangue , Genótipo , Humanos , Desempenho Psicomotor/fisiologia
2.
Yakugaku Zasshi ; 139(11): 1397-1402, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31685736

RESUMO

Patients with epilepsy are often affected by not only seizures but also a variety of cognitive and psychiatric comorbidities that further impair their quality of life. However, it is unclear whether epilepsy is associated with psychic function. The aim of the present study was to clarify the effects of kindling-induced epileptic seizures on psychic functioning, using behavioral pharmacological tests. Pentylenetetrazol (PTZ)-kindled mice displayed impaired motor coordination (in the rotarod test), and social approach impairment (in the three-chamber social test) compared with vehicle mice. Intraperitoneal ABT-418 treatment (0.05 mg/kg) alleviated these behavioral abnormalities in PTZ-kindled mice. Immunolabeling of tissue sections demonstrated that expression of the α4 subunit of the α4ß2 nicotinic acetylcholine receptor in the piriform cortex was significantly decreased in PTZ-kindled mice. In contrast, expression of the synaptic adhesion molecule neuroligin 3 (NLG3) was significantly higher in the piriform cortex of PTZ-kindled mice compared with vehicle mice. Collectively, our findings suggest that attention deficit/hyperactivity disorder (ADHD)-like or autistic-like behavioral abnormalities associated with epilepsy are closely linked to downregulation of the α4 subunit of the α4ß2 receptor and upregulation of NLG3 in the mouse piriform cortex. In summary, this study indicates that ABT-418 is a good candidate for the treatment of patients with epilepsy complicated by psychiatric symptoms such as autism and ADHD.


Assuntos
Epilepsia/psicologia , Excitação Neurológica , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/etiologia , Pentilenotetrazol , Receptores Nicotínicos/metabolismo , Convulsões/psicologia , Animais , Moléculas de Adesão Celular Neuronais/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Isoxazóis/farmacologia , Isoxazóis/uso terapêutico , Proteínas de Membrana/metabolismo , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Córtex Piriforme/metabolismo , Desempenho Psicomotor/efeitos dos fármacos , Pirrolidinas/farmacologia , Pirrolidinas/uso terapêutico , Qualidade de Vida , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/etiologia , Comportamento Social
3.
World Neurosurg ; 132: e99-e108, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31518751

RESUMO

BACKGROUND: High cholesterol has been correlated with a greater risk of cerebrovascular diseases. Whether pre-existing high cholesterol exacerbates traumatic brain injury (TBI), and whether treatment with the cholesterol-lowering agent simvastatin has neuroprotective effects, especially anti-neuroinflammatory effects, after TBI are not well investigated. METHODS: Five-week-old male Sprague-Dawley rats were fed a high-fat diet for 8 weeks to induce hypercholesterolemia. Anesthetized male Sprague-Dawley rats were divided into 5 groups, including the sham-operated control, TBI control, and TBI with simvastatin treatment (4 mg/kg, 10 mg/kg, or 20 mg/kg) groups. Simvastatin was intraperitoneally injected at 0, 24, and 48 hours after TBI. Motor function was measured using an inclined plane. Neuronal apoptosis (maker Neu-N, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling), tumor necrosis factor-α expression in microglia (marker OX42) and astrocytes (marker glial fibrillary acidic protein), and Tumor necrosis factor-alpha receptor (TNFR) 1 and TNFR2 expression in neurons in the ischemic cortex were investigated using an immunofluorescence assay. All of the parameters were measured on the third day after TBI. RESULTS: TBI significantly increased the serum levels of cholesterol. The TBI-induced motor deficit was significantly attenuated by 4, 10, and 20 mg/kg simvastatin therapy on the third day after TBI. TBI-induced neuronal TNFR1 activation and apoptosis, as well as tumor necrosis factor-α expression in astrocytes in the ischemic cortex, were significantly attenuated by simvastatin, particularly when 20 mg/kg was administered. Simultaneously, the serum cholesterol remained high despite simvastatin treatment. CONCLUSIONS: The neuroprotection effects of simvastatin on the pre-existing hypercholesterolemia during TBI in rats may be related to its anti-neuroinflammatory effects but not to its cholesterol-lowing effects.


Assuntos
Anticolesterolemiantes/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/etiologia , Fármacos Neuroprotetores/uso terapêutico , Sinvastatina/uso terapêutico , Animais , Lesões Encefálicas Traumáticas/psicologia , Colesterol/sangue , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Necrose Tumoral/biossíntese , Fator de Necrose Tumoral alfa/sangue
5.
Psychopharmacology (Berl) ; 236(8): 2501-2512, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31302719

RESUMO

RATIONALE: Although methylphenidate and other stimulants have been demonstrated to improve task performance across a variety of domains, a computationally rigorous account of how these drugs alter cognitive processing remains elusive. Recent applications of mathematical models of cognitive processing and electrophysiological methods to this question have suggested that stimulants improve the integrity of evidence accumulation processes for relevant choices, potentially through catecholaminergic modulation of neural signal-to-noise ratios. However, this nascent line of work has thus far been limited to simple perceptual tasks and has largely omitted more complex conflict paradigms that contain experimental manipulations of specific top-down interference resolution processes. OBJECTIVES AND METHODS: To address this gap, this study applied the conflict linear ballistic accumulator (LBA), a newly proposed model designed for conflict tasks, to data from healthy adults who performed the Multi-Source Interference Task (MSIT) after acute methylphenidate or placebo challenge. RESULTS: Model-based analyses revealed that methylphenidate improved performance by reducing individuals' response thresholds and by enhancing evidence accumulation processes across all task conditions, either by improving the quality of evidence or by reducing variability in accumulation processes. In contrast, the drug did not reduce bottom-up interference or selectively facilitate top-down interference resolution processes probed by the experimental conflict manipulation. CONCLUSIONS: Enhancement of evidence accumulation is a biologically plausible and task-general mechanism of stimulant effects on cognition. Moreover, the assumption that methylphenidate's effects on behavior are only visible with complex executive tasks may be misguided.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Simulação por Computador , Metilfenidato/farmacologia , Modelos Psicológicos , Desempenho Psicomotor/efeitos dos fármacos , Adolescente , Adulto , Cognição/efeitos dos fármacos , Cognição/fisiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Adulto Jovem
6.
J Clin Psychopharmacol ; 39(5): 489-493, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31305338

RESUMO

PURPOSE: We aimed to study the pharmacokinetics of methadone and buprenorphine in blood and oral fluid after single-dose administration and investigate correlations between concentrations in blood and neurocognitive functions. METHODS: A 5-way, double-blind, randomized, placebo-controlled, double-dummy, crossover study was performed to study the pharmacokinetics and neurocognitive effects of methadone (5 and 10 mg per oral) and buprenorphine (0.2 and 0.4 mg sublingual) in 22 healthy volunteers. Blood and oral fluid were collected throughout the test days, and drug concentrations in both matrices were analyzed using ultrahigh-performance liquid chromatography-tandem mass spectrometry. On-road driving testing, neurocognitive computerized tests, and subjective questionnaires were performed. RESULTS: Large individual variations in concentrations of methadone and buprenorphine in blood and oral fluid, and accordingly oral fluid/blood drug concentration ratios, were observed. The mean ratio 6.5 hours after drug administration was 2.0 (range, 0.49-7.39) for methadone after both doses. Buprenorphine was not detected above the limit of quantification in blood after 6.5 hours. No significant correlation between methadone concentration in blood and effect was found. Significant correlations were found between buprenorphine concentration in blood and standard deviation of lateral position in the driving test and some measures of reaction time, divided attention, balance, alertness, contentedness. and sleepiness. CONCLUSIONS: Concentrations of methadone and buprenorphine in blood and oral fluid showed large interindividual variations. No concentration-effect correlations were found for methadone, whereas low to moderate correlations were observed between buprenorphine concentration and driving, psychomotor function, and subjective rating of sleep and alertness.


Assuntos
Analgésicos Opioides/administração & dosagem , Buprenorfina/administração & dosagem , Cognição/efeitos dos fármacos , Metadona/administração & dosagem , Desempenho Psicomotor/efeitos dos fármacos , Administração Oral , Administração Sublingual , Adulto , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/farmacologia , Condução de Veículo , Buprenorfina/farmacocinética , Buprenorfina/farmacologia , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Metadona/farmacocinética , Metadona/farmacologia , Pessoa de Meia-Idade , Tempo de Reação/efeitos dos fármacos , Espectrometria de Massas em Tandem , Adulto Jovem
7.
Eur J Pharmacol ; 858: 172497, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31238066

RESUMO

Metformin, an AMP-activated protein kinase (AMPK) activator, is an oral hypoglycemic drug widely used to treat patients with type 2 diabetes. As AMPK plays a role in the nociceptive processing, investigating the effects induced by metformin in experimental models of pain is warranted. In the present study, we further evaluated the effects induced by metformin in models of nociceptive and neuropathic pain and investigated mechanisms that could mediate such effects. Metformin was administered per os (p.o.) in mice. Nociceptive response induced by heat (hot-plate) and mechanical allodynia induced by chronic constriction injury (CCI) were used as pain models. Naltrexone (intraperitoneal) and glibenclamide (p.o.) were used to investigate mechanisms mediating metformin effects. A single administration of metformin (500 or 1000 mg/kg) inhibited the nociceptive response in the hot-plate model. Single and repeated administration of metformin (250, 500 or 1000 mg/kg) inhibited the mechanical allodynia induced by CCI. Metformin (250, 500 or 1000 mg/kg) did not affect the time mice spent in the rota-rod apparatus. The activity of metformin (1000 mg/kg) in both pain models was attenuated by naltrexone (10 mg/kg), but not by glibenclamide. Concluding, metformin exhibited activity in models of nociceptive and neuropathic pain. In the model of neuropathic pain, preventive and therapeutic effects were observed. Activation of opioidergic pathways partially mediates metformin antinociceptive activity. Altogether, the results indicate that metformin should be further investigated aiming its repositioning in the treatment of patients with different painful conditions.


Assuntos
Analgésicos/farmacologia , Metformina/farmacologia , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Nociceptividade/efeitos dos fármacos , Receptores Opioides/metabolismo , Analgésicos/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Glibureto/farmacologia , Hiperalgesia/tratamento farmacológico , Metformina/uso terapêutico , Camundongos , Naltrexona/farmacologia , Neuralgia/fisiopatologia , Desempenho Psicomotor/efeitos dos fármacos
8.
Chemosphere ; 235: 12-20, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31254777

RESUMO

Detection of developmental neurotoxicity (DNT) has been recognized as a major challenge by regulatory bodies and science. In search of sensitive and specific test methods, spontaneous tail coiling of embryonic zebrafish has been recommended as a promising tool for identification of DNT-inducing chemicals. The present study was designed to develop a protocol for a prolonged test to study neurotoxicity during the entire development of coiling movement in zebrafish embryos. Ambient illumination was found to modulate coiling activity from the very onset of tail movements representing the earliest behavioral response to light possible in zebrafish. In the dark, embryos displayed increased coiling activity in a way known from photokinesis, a stereotypical element of the visual motor response. Elevated coiling activity during dark phases allows for the development of test strategies that integrate later coiling movements under the control of a further developed nervous system. Furthermore, zebrafish embryos were exposed to ethanol, and coiling activity was analyzed according to the new test protocol. Exposure of embryos to non-teratogenic concentrations of ethanol (0.4-1%) resulted in a delay of the onset of coiling activity and heartbeat. Moreover, ethanol produced a dose-dependent increase in coiling frequency at 26 h post-fertilization, indicating the involvement of neurotoxic mechanisms. Analysis of coiling activity during prolonged exposure allowed for (1) attributing effects on coiling activity to different mechanisms and (2) preventing false interpretation of results. Further research is needed to verify the potential of this test protocol to distinguish between different mechanisms of neurotoxicity.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Etanol/toxicidade , Síndromes Neurotóxicas/etiologia , Animais , Etanol/farmacologia , Síndromes Neurotóxicas/embriologia , Desempenho Psicomotor/efeitos dos fármacos , Cauda/fisiopatologia , Peixe-Zebra/embriologia , Peixe-Zebra/crescimento & desenvolvimento
9.
Psychopharmacology (Berl) ; 236(11): 3341-3352, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31201479

RESUMO

RATIONALE: Dozens of preclinical studies have reported cannabinoid agonist potentiation of the analgesic effects of µ-opioid agonists. OBJECTIVES: The aim of this study was to determine if a cannabinoid agonist could potentiate opioid analgesia in humans using several laboratory pain models. METHODS: Healthy participants (n = 10) with/out current drug use/pain conditions completed this within-subject, double-blind, placebo-controlled, randomized outpatient study. Nine 8-h sessions were completed during which dronabinol (0, 2.5, 5 mg, p.o.) was administered 1 h before oxycodone (0, 5, 10 mg, p.o.) for a total of 9 test conditions. Outcomes included sensory threshold and tolerance from four experimental pain models (cold pressor, pressure algometer, hot thermode, cold hyperalgesia), along with participant- and observer-rated, performance and physiological effects. RESULTS: Oxycodone produced miosis (p < 0.05) and analgesic responses (e.g., pressure algometer [p < 0.05]), while dronabinol did not (p > 0.05). Depending on the dose combination, dronabinol attenuated or did not alter oxycodone analgesia; for example, dronabinol (2.5 mg) decreased the analgesic effects of oxycodone (10 mg) on pressure tolerance. Conversely, dronabinol increased oxycodone subjective effects (e.g., drug liking) (p < 0.05); oxycodone (5 mg) ratings of "high" were potentiated by 5 mg dronabinol (p < 0.05; placebo = 1.1 [± 0.7]; 5 mg oxycodone = 4.7 [± 2.2]; 5 mg dronabinol = 9.9 [± 8.4]; 5 mg oxycodone + 5 mg dronabinol = 37.4 [± 11.3]). CONCLUSIONS: This study indicates that dronabinol did not enhance the analgesic effects of oxycodone and increased abuse- and impairment-related subjective effects. These data suggest that dronabinol may not be an effective or appropriate opioid adjuvant; it could potentially increase opioid dose requirements, while increasing psychoactive opioid effects.


Assuntos
Analgesia/métodos , Analgesia/psicologia , Analgésicos Opioides/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Medição da Dor/efeitos dos fármacos , Medição da Dor/psicologia , Adolescente , Adulto , Analgésicos Opioides/uso terapêutico , Agonistas de Receptores de Canabinoides/uso terapêutico , Estudos Cross-Over , Autoavaliação Diagnóstica , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor/psicologia , Medição da Dor/métodos , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Adulto Jovem
10.
Forensic Sci Int ; 301: 137-141, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31153990

RESUMO

Etizolam is a drug from the thienotriazoldiazepine class, widely prescribed as anxiolytic due to its apparently secure toxicological profile. Nevertheless, some recent cases of etizolam dependence, intoxications and fatalities associated to its abuse have been reported in the international literature. For this reason, the drug listed as new psychoactive substance (NPS) by the World Health Organization (WHO) since 2015. Euphoric effect at high dosage is the first cause of its recreational use that has determined a wider distribution in the illicit market. An experimental study was performed to obtain evidence that etizolam at low therapeutic dosages is a drug with negligible influence on the psychomotor performances involved in driving. The psychomotor performance was assessed by performing different tests, such as critical tracking task (CTT), critical flicker fusion (CFF), choice reaction time (CRT), visual vigilance task (VVT), response competition test (RCT) in a group of 16 healthy volunteers after a single administration of etizolam at two different dosages (0.25 mg or 1.00 mg) in comparison to placebo. The test results showed that etizolam at 0.25 mg and 1.00 mg had no significant effect on vigilance, short term memory, psychomotor coordination or speed in decision making. Differently, abuse of etizolam to obtain the euphoric effects at presumably high dosages or in combination with other psychoactive substances could be fatal. The negligible side effects on mental and behavioral function demonstrated by this study, could represent an incitement to abuse, which can be strongly discouraged with correct information on differences between its correct use and its misuse.


Assuntos
Diazepam/análogos & derivados , Desempenho Psicomotor/efeitos dos fármacos , Tranquilizantes/administração & dosagem , Adulto , Estudos Cross-Over , Tomada de Decisões/efeitos dos fármacos , Diazepam/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Testes Neuropsicológicos , Tempo de Reação/efeitos dos fármacos , Adulto Jovem
11.
Ergonomics ; 62(8): 1023-1032, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31045484

RESUMO

Military and law enforcement personnel are required to maintain optimal marksman accuracy and reaction time during extended duty hours amidst environmental stressors. Although caffeine is commonly used to mitigate the consequences of fatigue, the effects of caffeine on marksmanship accuracy are inconclusive. The purpose of this review was to determine the effect of caffeine on marksman accuracy and reaction time. A literature search was conducted and 17 articles were selected for review based on relevance and methodological quality. Caffeine consistently improved marksman reaction time but did not improve marksmanship accuracy. However, there is some evidence that caffeine attenuates performance decrements in marksman accuracy caused by stress and fatigue if optimal dosing strategies are employed. Dosing strategies timed according to hours of wakefulness and time before testing could prevent performance deterioration. Doses of 100-200 mg every 2 hours may effectively improve accuracy during extended duty; however, further research is needed. Practitioner Summary: The purpose of this review was to determine the effect of caffeine on marksman accuracy and reaction time. A literature search was conducted and 17 articles were selected for review based on relevance and methodological quality. Caffeine consistently improved marksman reaction time but did not improve marksmanship accuracy.


Assuntos
Cafeína/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Militares/psicologia , Polícia/psicologia , Tempo de Reação/efeitos dos fármacos , Análise e Desempenho de Tarefas , Adulto , Feminino , Humanos , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Vigília/efeitos dos fármacos
12.
Eur J Pharmacol ; 856: 172408, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31129158

RESUMO

Painful diabetic neuropathy (PDN) is a serious symptom that compromises quality of life and remains without effective pharmacological treatment. The transient receptor vanilloid 4 (TRPV4) is a cation-permeable channel implicated in sensory transduction and pain signalling. Therefore, drugs that act on TRPV4 may have therapeutic applications to treat PDN. In the present work, we assessed the effect of the selective TRPV4 channel antagonist HC-067047 on painful neuropathy associated with streptozotocin (STZ)-induced diabetes in mice. STZ-treated animals presented both mechanical and cold allodynia at 6 weeks after diabetes induction. Notably, HC-067047 (1 mg/kg, s.c.) given daily between 2 and 6 weeks after diabetes induction significantly prevented the development of mechanical allodynia. Additionally, both single and repeated treatments with HC-067047 (10 mg/kg, s.c.) significantly reverted established mechanical allodynia induced by STZ. However, HC-067047 was not capable of affecting either thermal cold allodynia or hyperglycemia. Similarly, HC-067047 treatments showed no effect on body weight, temperature, locomotor activity or motor coordination of control mice. Immunohistochemistry assay showed that TRPV4 expression was not different in sciatic nerve, dorsal root ganglia (DRG) or hind paw plantar skin from diabetic and non-diabetic mice, suggesting that HC-067047 acts on constitutive receptors to inhibit mechanical allodynia. Taken together, the data generated in the present study show the potential relevance of using TRPV4 antagonists to treat painful neuropathy associated with diabetes.


Assuntos
Neuropatias Diabéticas/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Morfolinas/farmacologia , Pirróis/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/fisiopatologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Morfolinas/uso terapêutico , Desempenho Psicomotor/efeitos dos fármacos , Pirróis/uso terapêutico , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Canais de Cátion TRPV/metabolismo
13.
Life Sci ; 228: 285-294, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31063733

RESUMO

AIMS: Oxidative stress and apoptosis have major roles in the progression of traumatic brain injury (TBI)-associated motor and cognitive deficits. The present study was aimed to elucidate the putative effects of chrysin, a natural flavonoid compound, against TBI-induced motor and cognitive dysfunctions and possible involved mechanisms. MAIN METHODS: Chrysin (25, 50 or 100 mg/kg) was orally administered to rats starting immediately following TBI induction by Marmarou's weight-drop technique and continuously for 3 or 14 days. Neurological functions, motor coordination, learning and memory performances, histological changes, cell apoptosis, expression of pro- and anti-apoptotic proteins, and oxidative status were assayed at scheduled time points after experimental TBI. KEY FINDINGS: The results indicated that treatment with chrysin improved learning and memory disabilities in passive avoidance task, and ameliorated motor coordination impairment in rotarod test after TBI. These beneficial effects were accompanied by increased the concentrations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), decreased malondialdehyde (MDA) content, prevented neuronal loss, diminished apoptotic index, elevated the expression of anti-apoptotic Bcl-2 protein, and reduced the expression of pro-apoptotic Bax protein in the cerebral cortex and hippocampus tissues. SIGNIFICANCE: Our findings suggest that both anti-oxidative and anti-apoptotic properties of chrysin (especially in the dose of 100 mg/kg) are possible mechanisms that improve cognitive/motor deficits and prevent neuronal cell death after TBI.


Assuntos
Antioxidantes/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Flavonoides/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/fisiopatologia , Modelos Animais de Doenças , Flavonoides/administração & dosagem , Aprendizagem/efeitos dos fármacos , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Ratos Wistar
14.
Oxid Med Cell Longev ; 2019: 4032428, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049134

RESUMO

Tolfenamic acid is a nonsteroidal anti-inflammatory drug with neuroprotective properties, and it alleviates learning and memory deficits in the APP transgenic mouse model of Alzheimer's disease. However, whether tolfenamic acid can prevent motor and memory dysfunction in transgenic animal models of Huntington's disease (HD) remains unclear. To this end, tolfenamic acid was orally administered to transgenic R6/1 mice from 10 to 20 weeks of age, followed by several behavioral tests to evaluate motor and memory function. Tolfenamic acid improved motor coordination in R6/1 mice as tested by rotarod, grip strength, and locomotor behavior tests and attenuated memory dysfunction as analyzed using the novel object recognition test and passive avoidance test. Tolfenamic acid decreased the expression of mutant huntingtin in the striatum of 20-week-old R6/1 mice by inhibiting specificity protein 1 expression and enhancing autophagic function. Furthermore, tolfenamic acid exhibited antioxidant effects in both R6/1 mice and PC12 cell models. Collectively, these results suggest that tolfenamic acid has a good therapeutic effect on R6/1 mice, and may be a potentially useful agent in the treatment of HD.


Assuntos
Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Doença de Huntington , Transtornos da Memória , Desempenho Psicomotor/efeitos dos fármacos , ortoaminobenzoatos/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Modelos Animais de Doenças , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Doença de Huntington/genética , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Doença de Huntington/prevenção & controle , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/genética , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Transtornos da Memória/prevenção & controle , Camundongos , Camundongos Transgênicos , Mutação , Células PC12 , Ratos
15.
Br J Anaesth ; 122(5): 671-681, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30982593

RESUMO

BACKGROUND: We hypothesised that exposure to multiple, but not single, procedures requiring general anaesthesia before age 3 yr is associated with a specific pattern of deficits in processing speed and fine motor skills. METHODS: A secondary analysis (using factor and cluster analyses) of data from the Mayo Anesthesia Safety in Kids study was conducted, in which unexposed, singly exposed, and multiply exposed children born in Olmsted County, MN, USA from 1994 to 2007 were sampled using a propensity-guided approach and underwent neuropsychological testing at ages 8-12 or 15-20 yr. RESULTS: In the factor analysis, the data were well fit to a five factor model. For subjects multiply (but not singly) exposed to anaesthesia, a factor reflecting motor skills, visual-motor integration, and processing speed was significantly lower [standardised difference of -0.35 (95% confidence interval {CI} -0.57 to -0.13)] compared with unexposed subjects. No other factor was associated with exposure. Three groups were identified in the cluster analysis, with 106 subjects (10.6%) in Cluster A (lowest performance in most tests), 557 (55.9%) in Cluster B, and 334 (33.5%) in Cluster C (highest performance in most tests). The odds of multiply exposed children belonging to Cluster A was 2.83 (95% CI: 1.49-5.35; P=0.001) compared with belonging to Cluster B; there was no other significant association between exposure status and cluster membership. CONCLUSIONS: Multiple, but not single, exposures to procedures requiring general anaesthesia before age 3 yr are associated with a specific pattern of deficits in neuropsychological tests. Factors predicting which children develop the most pronounced deficits remain unknown.


Assuntos
Anestesia Geral/efeitos adversos , Anestésicos Gerais/efeitos adversos , Transtornos do Neurodesenvolvimento/induzido quimicamente , Desempenho Psicomotor/efeitos dos fármacos , Adolescente , Fatores Etários , Anestésicos Gerais/administração & dosagem , Anestésicos Gerais/farmacologia , Criança , Análise por Conglomerados , Análise Fatorial , Feminino , Humanos , Masculino , Destreza Motora/efeitos dos fármacos , Testes Neuropsicológicos , Fatores de Risco , Adulto Jovem
16.
PLoS One ; 14(4): e0215612, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002681

RESUMO

Understanding the effects of cognitive enhancing drugs is an important area of research. Much of the research, however, has focused on restoring memory following some sort of disruption to the brain, such as damage or injections of scopolamine. Aniracetam is a positive AMPA-receptor modulator that has shown promise for improving memory under conditions when the brain has been damaged, but its effectiveness in improving memory in neurologically healthy subjects is unclear. The aim of the present study was to examine the effects of aniracetam (100mg/kg and 200 mg/kg) on short-term memory in "neurologically healthy" pigeons. Pigeons were administered aniracetam via either intramuscular injection or orally, either 30 or 60 minutes prior to testing on a delayed matching-to-sample task. Aniracetam had no effect on the pigeons' memory performance, nor did it affect response latency. These findings add to the growing evidence that, while effective at improving memory function in models of impaired memory, aniracetam has no effect in improving memory in healthy organisms.


Assuntos
Encéfalo/efeitos dos fármacos , Columbidae/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Pirrolidinonas/farmacologia , Administração Oral , Animais , Encéfalo/fisiologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Injeções Intramusculares , Memória de Curto Prazo/fisiologia , Nootrópicos/administração & dosagem , Nootrópicos/farmacocinética , Nootrópicos/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Pirrolidinonas/administração & dosagem , Pirrolidinonas/farmacocinética , Fatores de Tempo
17.
Pharmacol Rep ; 71(3): 466-472, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31003159

RESUMO

BACKGROUND: ß2-Adrenergic receptor agonists are widely used agents in the treatment of asthma or preterm labor. Since prevalence of asthma was shown to be higher in patients with epilepsy and modulation of noradrenergic system activity may modify epilepsy course, the aim of the present study was to examine the effect of salbutamol (SALB), one of the most commonly used ß2-adrenergic receptor agonist on the anticonvulsant potency of four classical antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB) in mice subjected to the maximal electroshock (MES)-induced seizures. METHODS: Seizures were caused by a current delivered through ear-clip electrodes. The influence of AEDs and SALB on animals' motor coordination and memory processes was also evaluated. RESULTS: Single SALB injection did not change, whereas 7 days SALB administration decreased seizure threshold in the MES-induced seizures in mice. Moreover, SALB injected ip for 1 day and for 7 days lowered the antiepileptic activity of PB in the MES-induced seizures in mice, but did not change the effect of other analyzed AEDs: VPA, CBZ or DPH. Butoxamine, a selective ß2-adrenergic receptor antagonist, reversed SALB influence on the activity of PB. SALB given alone or in combination with the tested AEDs did not affect animals' motor performance and memory after both single and 7 days administration. CONCLUSIONS: Presented results show that SALB may decrease the antiepileptic efficacy of PB. A special caution is advised to patients with epilepsy receiving ß2-adrenergic receptors agonists in the pharmacotherapy of pulmonary and obstetrical disorders.


Assuntos
Albuterol/farmacologia , Anticonvulsivantes/farmacologia , Convulsões/tratamento farmacológico , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações de Medicamentos , Eletrochoque/métodos , Masculino , Memória/efeitos dos fármacos , Camundongos , Desempenho Psicomotor/efeitos dos fármacos
18.
Neurobiol Learn Mem ; 161: 169-174, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31022446

RESUMO

Studies investigating effects of acute stress on Prospective Memory (PM) so far yielded heterogeneous findings. Although results were commonly attributed to stress-induced changes in cortisol, past research did not disentangle effects of cortisol from the effects of sympathetic nervous system (SNS) activation and cognitive reappraisal. The present study therefore aimed at investigating the mere effect of cortisol on PM tasks that differently involve prefrontal brain regions (nonfocal vs. focal PM tasks) via a placebo-controlled oral pharmacological intake of 10 mg hydrocortisone mimicking physiological responses to stress. Contrary to our prediction, enhanced levels of cortisol did not affect PM accuracy and monitoring costs, neither for the focal nor the nonfocal PM tasks. These results suggest that changes of cortisol levels do not underlie potential stress effects on PM. Further exploratory results revealed that PM performance was higher in the 3 pm than in the 1 pm placebo group. This means that PM performance, independently of effects of cortisol, seem to vary throughout the day.


Assuntos
Adaptação Psicológica/fisiologia , Ritmo Circadiano/fisiologia , Glucocorticoides/farmacologia , Hidrocortisona/farmacologia , Memória Episódica , Desempenho Psicomotor/fisiologia , Estresse Psicológico/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adaptação Psicológica/efeitos dos fármacos , Adulto , Ritmo Circadiano/efeitos dos fármacos , Método Duplo-Cego , Feminino , Glucocorticoides/administração & dosagem , Humanos , Hidrocortisona/administração & dosagem , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Estresse Psicológico/metabolismo , Sistema Nervoso Simpático/metabolismo , Adulto Jovem
19.
Neurobiol Learn Mem ; 161: 51-56, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30862525

RESUMO

The rodent odor span task (OST) uses an incrementing non-matching to sample procedure in which a series of odors is presented and selection of the session-novel odor is reinforced. An OST is frequently used to test the effects of neurobiological variables on memory capacity as the number of odors to remember increases during the course of the session. In this regard, one important finding has been that NMDA receptor antagonists selectively impair OST performance at doses that spare accuracy on control tasks. However, in many versions of the odor span task the number of stimuli to remember is confounded with the number of distractor odors presented to the rat on each trial. The present study compared the effects of the NMDA antagonist dizocilpine when the number of choices was held constant at two (one novel odor-S+ and one previously presented distractor odor-S-) and when the number of choice stimuli was permitted to increase up to 10 (one S+ and 9 S-). Dizocilpine impaired OST accuracy at doses that had no effect on a reference memory control task in both 2-choice and 10-choice conditions; however, the dose-response function was shifted to the left in the 10-choice tests. The impairments produced by dizocilpine were exacerbated as the memory load increased in both 2- and 10-choice conditions. These findings support the hypothesis that NMDA antagonism reduces the number of stimuli that rats can remember accurately, but the interaction between the effective DZP dose and the number of distractors shows that drug effects on OST performances may involve attentional factors in addition to memory capacity. The findings also demonstrate that variations in number of OST distractors can be used to alter sensitivity of the task.


Assuntos
Atenção , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Memória de Curto Prazo , Percepção Olfatória , Desempenho Psicomotor , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Atenção/efeitos dos fármacos , Atenção/fisiologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Percepção Olfatória/efeitos dos fármacos , Percepção Olfatória/fisiologia , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Ratos , Ratos Sprague-Dawley
20.
Psychiatry Res ; 275: 31-38, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878854

RESUMO

Schizophrenia (SCZ) patients show deficits in many domains, including cognition and perception. However, results are often mixed. One reason for mixed results may be differences in medication. Very little is known about the role of medication in visual processing. Here, we investigated the effects of typical vs. atypical medication on contrast sensitivity (spatial frequencies ranging from 0.2 to 20 cycles per degree), vernier acuity, and visual backward masking. From a large pool of patients, we selected 50 patients (Study 1, conducted in Brazil) and 97 patients (Study 2, conducted in Georgia) taking either only typical or atypical medication. Patients with atypical medication performed significantly better than patients with typical medication for contrast sensitivity, vernier duration, and backward masking. As a secondary result, we found similar, but not significant, trends for the cognitive tasks (Stroop, Flanker, Trail-Making Test-B, Wisconsin Card Sorting Test and Continuous Performance Test) in the same patients. No correlations were found between demographics, psychopathology, chlorpromazine equivalents and visual processing. A conclusion of our study is that one needs to be careful comparing studies when medication is not comparable.


Assuntos
Antipsicóticos/uso terapêutico , Mascaramento Perceptivo , Desempenho Psicomotor/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Percepção Visual/efeitos dos fármacos , Adulto , Antipsicóticos/farmacologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor/fisiologia , Esquizofrenia/diagnóstico , Teste de Sequência Alfanumérica , Percepção Visual/fisiologia
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