Subchronic 3, 4-methylenedioximethamphetamine (mdma) reverts anxiety induced by chronic mild stress

Here we report the effects of subchronic 3, 4-Methylenedioximethamphetamine (MDMA) on the elevated plus-maze, a widely used animal model of anxiety. Rats exposed to a mild chronic stress (MCS) protocol received intracerebroventricular microinjections of the selective serotonin reuptake inhibitor (SSRI) – fluoxetine (2.0ug/ul) or 3, 4-Methylenedioximethamphetamine (MDMA, 2.0ug/ul) for seven days. On the eighth day rats were tested in the elevated plus-maze. Our results showed that sub-chronic MDMA interacted with MCS leading to a decrease in anxiety-related behaviors including: percentage of open arms entries (F[2,26]=4.00; P=0.031), time spent in the open arms (F[2,26]=3.656; P=0.040) and time spent in the open arms extremities (F[2,26]=5.842; P=0.008). These results suggest a potential effect of MDMA in the reversion of the emotional significance of aversive stimuli.

Neurobiology of expectancy effects and omission of reinforcement on behavior

The reinforcement omission effects have been traditionally interpreted in terms of: behavioral facilitation after reinforcement omission induced by primary frustration or behavioral suppression after reinforcement delivery induced by postconsummatory states. The studies reviewed here indicate that amygdala is involved in modulation of these effects. However, the fact that amygdala lesions, extensive or selective, can eliminate, reduce and enhance the omission effects makes it difficult to understand how it is the exact nature of their involvement. The amygdala is related to several functions that depend on its connections with other brain systems. Thus, it is necessary to consider the involvement of a more complex neural network in the modulation of the reinforcement omission effects. The connection of amygdala subareas to cortical and subcortical structures may be involved in this modulation since they also are linked to processes related to reward and expectancy.

Molecular mechanism involved in the mutagenicity induced by Aflatoxin B1

The aflatoxin B1 (AFB1) is a mycotoxin that has been identified as the most potent hepatocarcinogen. The metabolite resulting from detoxification process of AFB1 in liver, has the ability to react with the genomic DNA, generating AFB1-DNA adducts; during DNA replication process, this adduct induced the G:C→T:A transversion. Polymorphism in genes encoding for enzymes involved in the activation and detoxification of AFB1 and DNA repair enzymes has been associated with the risk of hepatocellular carcinoma (HCC) development. Additionally, in populations of high exposure to aflatoxin and high prevalence of hepatitis B virus (HBV) infection, has been demonstrated a synergism between these two risk factors for the development of HCC.

Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.