Macarena Moreno

The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However, several clinical trials are investigating MOD as an alternative pharmacological treatment for attentional deficit and hyperactivity disorder (ADHD) in children and adolescents. On the other hand, the early use of psychostimulants and the misdiagnosis rates in ADHD make it crucial to investigate the brain effects of this type of drug in young healthy individuals. The aim of this work was to evaluate the effects of chronic MOD treatment on neurochemicals (γ-aminobutyric acid and glutamate), dopamine receptor 2 (D₂) expression and behavior (non-selective attention “NSA”) in the mesocorticolimbic system of young healthy Sprague–Dawley rats. Preadolescent male rats were injected with MOD (75 mg/kg, i.p.) or a vehicle for 14 days (from postnatal day 22 to 35). At postnatal day 36, we measured the GLU and GABA contents and their extracellular levels in the nucleus accumbens (NAc). In addition, the GLU and GABA contents were measured in the ventral tegmental area (VTA) and D₂ protein levels in the prefrontal cortex (PFC). Chronic use of MOD during adolescence induces behavioral and neurochemical changes associated with the mesocorticolimbic system, such as a reduction in PFC D₂ expression, VTA GABA levels and NSA. These results contribute to the understanding of the neurological effects of chronic MOD use on a young healthy brain.

Oxytocin (OT) and vasopressin (AVP) are hypothalamic neuropeptides classically associated with their regulatory role in reproduction, water homeostasis, and social behaviors. Interestingly, this role has expanded in recent years and has positioned these neuropeptides as therapeutic targets for various neuropsychiatric diseases such as autism, addiction, schizophrenia, depression, and anxiety disorders. Due to the chemical-physical characteristics of these neuropeptides including short half-life, poor blood-brain barrier penetration, promiscuity for AVP and OT receptors (AVP-R, OT-R), novel ligands have been developed in recent decades. This review summarizes the role of OT and AVP in neuropsychiatric conditions, as well as the findings of different OT-R and AVP-R agonists and antagonists, used both at the preclinical and clinical level. Furthermore, we discuss their possible therapeutic potential for central nervous system (CNS) disorders.

Los modelos de comportamiento permiten predecir la condición de deterioro de un pavimento y el desarrollo de programas de mantenimiento. Normalmente cuando se evalúa el desempeño de un pavimento a través del modelo de deterioro, el pronóstico corresponde a un valor determinista. Sin embargo, los proyectos de ingeniería de pavimentos tienen un grado de incertidumbre, lo que implica que el adecuado desempeño de la solución no puede ser totalmente asegurado. El objetivo de esta investigación es el de incorporar la probabilidad en el pronóstico del modelo de agrietamiento estructural, para lo cual se utilizó el modelo de iniciación y progresión del agrietamiento del programa HDM-4 bajo diferentes escenarios, definidos según la ubicación geográfica, tránsito y capacidad estructural de carreteras chilenas. Para incorporar la probabilidad en el modelo de comportamiento, se desarrolló un simulador que reproduce el deterioro para un ciclo de veinticinco años de vida, en el cual las variables descriptivas del modelo de comportamiento se representan como variables aleatorias gracias a datos recolectados en terreno. La investigación entrega como resultado una serie de funciones de densidad de probabilidad que representan la respuesta probabilística del modelo de deterioro de catorce grupos de rutas chilenas.