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1.
Toxicol Lett ; 344: 1-10, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33647392

RESUMO

Methylphenidate (MPD) is used as a first-line treatment for attention-deficit/hyperactivity disorder (ADHD). The number of prescriptions for ADHD patients is increasing, suggesting that the number of fertile women using such medication might be also increasing. The purpose of this study was to clarify the effects of MPD exposure during the fetal period on infant development, behavior, learning, and memory in mice. Expression levels of candidate genes associated with ADHD were also determined in the brain of pups born to MDP-treated dams who were administered MPD orally at a dose of 2.5, 7.5, or 15 mg/kg daily from gestational day 1 to the day before delivery. Offspring aged 6-8 weeks were subjected to the spontaneous locomotor activity, elevated plus-maze, and passive avoidance tests and therapeutic treatments with MPD or atomoxetine. Fetal MPD exposure induced ADHD-like phenotypes, such as hyperactivity and impulsivity, in mouse offspring, which were suppressed by treatment with MPD and atomoxetine. These mice showed decreased Drd2 and Slc6a3 expression levels in the brain, which are often observed in ADHD model animals. Our results suggest that continuous use of MPD during pregnancy induces ADHD phenotypes in the offspring.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Metilfenidato/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Receptores de Dopamina D2/metabolismo , Animais , Animais Recém-Nascidos , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Aprendizagem , Masculino , Metilfenidato/administração & dosagem , Camundongos , Camundongos Endogâmicos ICR , Gravidez , Receptores de Dopamina D2/genética
2.
J Toxicol Sci ; 44(12): 849-857, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31813904

RESUMO

Abuse of recreational drugs (i.e., synthetic chemicals with the structure or expected neurotropic effects, or both, similar to those of controlled substances) is a serious and continuous social harm. Designer drugs are often manufactured or synthesized in small-scale clandestine laboratories with impure starting materials, poor handling skills and inferior storage conditions. Therefore, in addition to the objective compound, diverse impurities may be present, for example, from the starting material, intermediates, catalytic metals formed during chemical synthesis, and materials from the environment. Impurity profiling of drug seizures is a useful scientific tool to obtain information on the clandestine manufacturers and drug trafficking networks. 1-Phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP), a novel psychoactive substance of the cathinone type that is banned in many countries, is still supplied and distributed within the illicit drug market. By using GC-MS and ICP-MS, we identified and estimated the relative contents of organic and inorganic impurities in the bulk powder of 15 batches of α-PVP. We then conducted multivariate data analyses to reveal characteristic patterns of the profiles. Hierarchical cluster analysis of both the organic and inorganic impurities revealed two groups that showed similar impurity profiles, which suggested that the batches in these groups were synthesized in similar routes under similar synthetic environments. The initial groups revealed by the organic impurities were further divided when combined with the data from the inorganic impurities. The present study, therefore, demonstrated the effectiveness of integrated analyses of organic and inorganic impurities for the accurate clustering of designer drugs, to provide precise information to drug investigation authorities.


Assuntos
Drogas Desenhadas/química , Contaminação de Medicamentos/legislação & jurisprudência , Compostos Inorgânicos/análise , Compostos Orgânicos/análise , Pentanonas/química , Pirrolidinas/química , Análise por Conglomerados , Controle de Medicamentos e Entorpecentes/métodos
3.
Anim Cogn ; 22(5): 707-718, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31127432

RESUMO

Relatively little is known about the ability of ungulates to visually discriminate vegetation patches while foraging on grasslands despite extensive studies with man-made stimuli presented indoors. This study aimed to assess visual discrimination ability of cattle (Bos taurus) under conditions closer to the actual foraging situation. Twelve Japanese Black cows were afforded four successive opportunities to choose between green and dead forages presented as 25 × 25 cm patches 1, 2, or 3 m ahead while walking through a 25-m-long field area. Apparatuses for presenting the forages as visual stimuli were designed to minimize olfactory cues. The green forage differed from the dead forage in appearance (color and texture) and quality (digestible dry matter and crude protein). Cows preferred the green forage to the dead forage and were able to use the forages as visual cues to discriminate them. The proportion of green forage choices was 0.70-0.72 (different from the chance at P < 0.001), 0.57 (P < 0.05), and 0.53 (P ≥ 0.1) at the distances of 1, 2, and 3 m, respectively. The results indicate that the ability of ungulates to visually discriminate vegetation patches during foraging in grasslands would not be as high as that expected from the visual acuity reported in the previous indoor studies.


Assuntos
Percepção de Cores , Comportamento Alimentar , Percepção Visual , Animais , Bovinos , Feminino
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