Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

The drastic increase in hallucinogenic compounds in illicit drug markets of new psychoactive substances (NPS) is a worldwide threat. Among these, 2, 5-dimetoxy-4-bromo-amphetamine (DOB) and paramethoxyamphetamine (PMA; marketed as "ecstasy") are frequently purchased on the dark web and consumed for recreational purposes during rave/dance parties. In fact, these two substances seem to induce the same effects as MDMA, which could be due to their structural similarities. According to users, DOB and PMA share the same euphoric effects: increasing of the mental state, increasing sociability and empathy. Users also experienced loss of memory, temporal distortion, and paranoia following the repetition of the same thought. The aim of this study was to investigate the effect of the acute systemic administration of DOB and PMA (0.01-30 mg/kg; i.p.) on motor, sensorimotor (visual, acoustic, and tactile), and startle/PPI responses in CD-1 male mice. Moreover, the pro-psychedelic effect of DOB (0.075-2 mg/kg) and PMA (0.0005-0.5 mg/kg) was investigated by using zebrafish as a model. DOB and PMA administration affected spontaneous locomotion and impaired behaviors and startle/PPI responses in mice. In addition, the two compounds promoted hallucinatory states in zebrafish by reducing the hallucinatory score and swimming activity in hallucinogen-like states

Estado del arte sobre los profesionales que egresan con tesis

La demora en la presentación de la tesis o la renuncia a llevarla a cabo, es un fenómeno que afecta a la mayoría de las universidades. Esto conlleva un bajo índice de graduación, constituyéndose en preocupación de las instituciones universitarias, al no poder alcanzar estándares de calidad determinados por la CONEAU y, al ver imposibilitado, en parte, su proyecto institucional, a la vez, retarda la inserción del egresado en el ámbito laboral específico, disminuye el rédito de la inversión en educación y, provoca cierto grado de frustración en el estudiante.La ponencia tiene por objeto exponer el estado del arte sobre los profesionales que egresan tras defender una tesis. Guarda relación con el Proyecto de Investigación de Desarrollo Anual, aprobado por la Universidad Autónoma de Entre Ríos titulado “La trayectoria del tesista.Un estudio en egresados de la UADER”, cuyo objetivo central es reconstruir la trayectoria del proceso de tesis en egresados de carreras de grado de dos de sus Facultades, identificando los elementos facilitadores y obstaculizadores del proceso de realización y finalización de la tesis.El corpus de análisis está conformado por más de cincuenta documentos en español e inglés, obtenidos, en su mayoría, de bases de datos de educación superior (ERIC, JSTOR, EBSCO), a partir de la década del ’90.En los estudios consultados aparecen, recurrentemente, factores relacionado a las tesis tales como: rol del director; evaluación; formación metodológica e interés del investigador por el tema; ocuparse en actividades no académicas de tipo económica, laboral; desconocimiento para aplicar el método científico; representaciones sociales estudiantiles sobre el trabajo final; contradicciones y falencias del sistema de educación superior; motivaciones; estrategias de estudio; conocimiento metacognitivo; competencias de escritura; conocimiento en computación e idiomas; organización del tiempo; comprensión de la metodología investigativa; teorías implícitas sobre las ciencias

A IMPORTÂNCIA DA AUDITORIA NOS ESTOQUES

Para avaliar a confiabilidade dos registros e das demonstrações contábeis, acontabilidade vale-se da auditoria, que nada mais é que o exame analítico e pericialseguido do desenvolvimento das operações contábeis, desde o início até o balanço.Este trabalho tem como objetivo mostrar a importância da auditoria dos estoqueslimitando-se apenas às técnicas de auditoria aplicadas. O estoque representa o custoacumulado dos materiais e produtos ainda não vendidos ou consumidos, relacionadoscom os objetivos e atividade da empresa, sendo importante na apuração do lucro decada exercício social. Cabe ressaltar que para algumas empresas o seu valor éinsignificante

Design and characterization of superpotent bivalent ligands targeting oxytocin receptor dimers via a channel-like structure

Dimeric/oligomeric states of G-protein coupled receptors have been difficult to target. We report here bivalent ligands consisting of two identical oxytocin-mimetics that induce a three order magnitude boost in G-protein signaling of oxytocin receptors (OTRs) in vitro and a 100- and 40-fold gain in potency in vivo in the social behavior of mice and zebrafish. Through receptor mutagenesis and interference experiments with synthetic peptides mimicking transmembrane helices (TMH), we show that such superpotent behavior follows from the binding of the bivalent ligands to dimeric receptors based on a TMH1-TMH2 interface. Moreover, in this arrangement, only the analogues with a well-defined spacer length (∼25 Å) precisely fit inside a channel-like passage between the two protomers of the dimer. The newly discovered oxytocin bivalent ligands represent a powerful tool for targeting dimeric OTR in neurodevelopmental and psychiatric disorders and, in general, provide a framework to untangle specific arrangements of G-protein coupled receptor dimers

Epileptiform Activity and Cognitive Deficits in SNAP-25+/− Mice are Normalized by Antiepileptic Drugs

Synaptosomal-associated protein of 25 kDa (SNAP-25) is a protein that participates in the regulation of synaptic vesicle exocytosis through the formation of the soluble NSF attachment protein receptor complex and modulates voltage-gated calcium channels activity. The Snap25 gene has been associated with schizophrenia, attention deficit hyperactivity disorder, and bipolar disorder, and lower levels of SNAP-25 have been described in patients with schizophrenia. We used SNAP-25 heterozygous (SNAP-25+/−) mice to investigate at which extent the reduction of the protein levels affects neuronal network function and mouse behavior. As interactions of genotype with the specific laboratory conditions may impact behavioral results, the study was performed through a multilaboratory study in which behavioral tests were replicated in at least 2 of 3 distinct European laboratories. Reductions of SNAP-25 levels were associated with a moderate hyperactivity, which disappeared in the adult animals, and with impaired associative learning and memory. Electroencephalographic recordings revealed the occurrence of frequent spikes, suggesting a diffuse network hyperexcitability. Consistently, SNAP-25+/− mice displayed higher susceptibility to kainate-induced seizures, paralleled by degeneration of hilar neurons. Notably, both EEG profile and cognitive defects were improved by antiepileptic drugs. These results indicate that reduction of SNAP-25 expression is associated to generation of epileptiform discharges and cognitive dysfunctions, which can be effectively treated by antiepileptic drug

Propuestas de actividades de enseñanza virtual del teatro para el Nivel Inicial y Primario.

Este cuadernillo busca recuperar las producciones de actividades pedagógicas de formación artística teatral destinadas a los niveles inicial y primario de las instituciones escolares. Fueron elaboradas durante julio y agosto de 2020 por estudiantes de la cátedra Práctica Docente III y Residencia en el Nivel Inicial y Primario del Profesorado de Teatro de la Facultad de Artes de la UNC. Estas producciones fueron pensadas dentro del contexto tan particular que nos tocó vivir (y que aún nos toca) debido a la pandemia mundial por el Covid-19. Las actividades que encontrarán en este cuadernillo se produjeron en un momento en el que las Prácticas y Residencias de los profesorados de la Facultad de Artes, tomamos la difícil decisión de posponer las Residencias hasta el 2021. Docentes y estudiantes aún nos estábamos conociendo sin saber quiénes éramos las personas que estábamos del otro lado de las pantallas. A las cátedras de Prácticas y Residencias nos estaba costando mucho retomar el contacto con les docentes orientadores y las instituciones asociadas con las que veníamos trabajando desde años anteriores.Fil: Altamirano, Ivana. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Brunetti, Cintia. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Drewniak, Abril. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Álvarez, Alexia. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Braida, Agustina. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Sidorowicz, Agustina. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Reyes, Carolina. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Copertari, Daniela. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Soria, Facundo. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Beltramone, Fátima. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Boero, Federico. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Vargas, María de los Ángeles. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Scándalo, Mariana. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Ferrer, Natacha. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Susperregui, Paula. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Ceballos, Susana. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Rizzo Veiga, Sol Merlina. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Elizondo, Tomás. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Vaccalluzzo, Victoria. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina.Fil: Bilikyan, Vilma. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Teatro; Argentina

[Re] construyendo el paisaje. Centro de interpretación

El proyecto se enmarca dentro de la recuperación de un sector del borde ribereño, un espacio degradado pero con alto valor ambiental y paisajístico. Hay allí una serie de humedales que están amenazados por el avance de un basural. Para ponerle fin a este problema y revitalizar ese espacio se propone un Centro de Interpretación del Paisaje. Esto contempla constituir una reserva ecológica-cultural que integre las funciones de observatorio y campo de experimentación científica y turismo ecológico.Fil: Baldassin, Daniela. Universidad Nacional de Rosario. Facultad de Arquitectura, Planeamiento y Diseño; Argentina.Fil: Braida, María Belén. Universidad Nacional de Rosario. Facultad de Arquitectura, Planeamiento y Diseño; Argentina

Neuroprotective Effects of Genistein in Mongolian Gerbils: Estrogen Receptor-β Involvement

Genistein is a naturally occurring plant-derived phytoestrogen, present in the human diet, known to possess some beneficial effects. The present study investigated the effect of genistein on neuroprotection evaluated through electroencephalographic and behavioural correlates in a model of global cerebral ischemia in gerbils. Over the dose range tested, genistein (3 and 10 mg/ kg), given 5 min after recirculation antagonized the ischemia-induced electroencephalographic total spectral power decrease 7 days after ischemia; fully prevented ischemia-induced hyperlocomotion evaluated 1 day after ischemia; reversed ischemia-induced memory impairment evaluated through both nest building behaviour and object recognition test; decreased malondialdehyde overproduction in the brain, evaluated 7 days after reperfusion; and fully promoted the survival of pyramidal cells in the CA1 hippocampal subfield. The selective antagonist for estrogen receptor–β (ERβ), 4-[2-phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP) given 30 min before carotid occlusion, fully prevented the neuroprotective effect of genistein at the dose of 3 mg/kg. These results demonstrate the neuroprotective effect of genistein through the activation of ERβ and provide further grounds for the growing interest concerning the true potential of phytoestrogens as compounds to beneficially affect brain injury without having the disadvantages of estrogens. Keywords:: ischemia, electroencephalography (EEG), phytoestrogen, CA1, estrogen receptor–

The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish

3,4-Methylenedioxymethamphetamine (MDMA) and its derivatives, 2,5-dimethoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA), are recreational drugs whose pharmacological effects have recently been attributed to serotonin 5HT2A/C receptors. However, there is growing evidence that the oxytocin (OT)/vasopressin system can modulate some the effects of MDMA. In this study, MDMA (2.5–10 mg/kg), DOB (0.5 mg/kg), or PMA (0.005, 0.1, or 0.25 mg/kg) were administered intramuscularly to adult zebra fish, alone or in combination with the V1a vasopressin antagonist, SR49059 (0.01–1 ng/kg), before carrying out conditioned place preference (CPP), social preference, novel tank diving, and light–dark tests in order to evaluate subsequent rewarding, social, and emotional-like behavior. The combination of SR49059 and each drug progressively blocked: (1) rewarding behavior as measured by CPP in terms of time spent in drug-paired compartment; (2) prosocial effects measured on the basis of the time spent in the proximity of a nacre fish picture; and (3) anxiolytic effects in terms of the time spent in the upper half of the novel tank and in the white compartment of the tank used for the light–dark test. Antagonism was obtained at SR49059 doses which, when given alone, did not change motor function. In comparison with a control group, receiving vehicle alone, there was a three to five times increase in the brain release of isotocin (the analog of OT in fish) after treatment with the most active doses of MDMA (10 mg/kg), DOB (0.5 mg/kg), and PMA (0.1 mg/kg) as evaluated by means of bioanalytical reversed-phase high-performance liquid chromatography. Taken together, these findings show that the OT/vasopressin system is involved in the rewarding, prosocial, and anxiolytic effects of MDMA, DOB, and PMA in zebra fish and underline the association between this system and the behavioral alterations associated with disorders related to substance abuse

Role of the endocannabinoid system in MDMA intracerebral self-administration in rats

I.c.v. self-administration of MDMA (0.01–2 μg per infusion), alone and in combination with CP 55,940 (0.4 μg infusion(−1)), was studied on an operant responding procedure. On the basis of individual preference for one of two levers, developed during training, rats were allowed to self-administer vehicle from the preferred lever and MDMA from the other. Pressings on the MDMA associated-lever, except for the maximal unit dose, progressively increased. The combination of CP 55,940 with MDMA (1 μg infusion(−1)) reduced the number of drug-associated lever pressings compared to the single drugs. Pre-treatment with SR 141716A (0.5 mg kg(−1) i.p.), 15 min before each daily session, significantly increased MDMA self-administration. These findings suggest that MDMA self-administration is under endogenous tonic control by the endocannabinoid system