ABSTRACT
Abstract Previous research has shown that exposure to nicotine and other drugs of abuse stimulate dopaminergic neurons in the mesolimbic circuit. Sustained activation of this circuit by prolonged exposure to drugs promotes locomotor sensitization. However, there are inconsistent reports about nicotine-induced locomotor sensitization when assessed among different developmental stages. We evaluated exploratory behavior on specific areas of the open field as an indicator of behavioral disinhibition and general locomotor activity as an indicator of nicotine-induced locomotor sensitization, to further explore the mechanisms underlying behavioral adaptations to nicotine exposure in animals from different developmental stages. We found that while adolescent and adult rats are equally responsive to nicotine-induced loco-motor sensitization, nicotine disrupts inhibition of risk-related behavior only in adolescent rats. Together, our results suggest that chronic daily exposure to nicotine promotes potentiation of its stimulant effects on locomotor activity. In adolescents, this effect is accompanied by a decreased capacity to inhibit risk-related behaviors under the acute effect of the drug.
Resumen Estudios previos han demostrado que exposición a la nicotina y otras drogas de abuso estimula las neuronas dopa-minérgicas del circuito mesolímbico. La activación sostenida de este circuito por exposición a las drogas promueve la sensibilización locomotriz. La evaluación de este efecto en diferentes etapas del desarrollo ha mostrado evidencia contradictoria sobre la susceptibilidad de adolescentes. En este trabajo exploramos las adaptaciones conductuales a la exposición crónica a nicotina en ratas adolescentes y adultas; para esto, evaluamos el comportamiento exploratorio en áreas específicas del campo abierto como indicador de desinhibición comportamental y el desplazamiento general como indicador de sensibilización locomotriz. Encontramos que, ambos grupos etarios muestran igual sensibilización locomotriz inducida por la nicotina y que la nicotina altera la inhibición del comportamiento relacionado con el riesgo sólo en adolescentes. Estos resultados sugieren que la exposición crónica diaria a la nicotina promueve la potenciación de sus efectos estimulantes sobre la actividad locomotriz y en los adolescentes, este efecto se acompana de una disminución de la capacidad para inhibir conductas relacionadas con el riesgo bajo el efecto agudo de la droga.
ABSTRACT
Alzheimer's disease (AD) is the most common senile dementia in the world. Although important progress has been made in understanding the pathogenesis of AD, current therapeutic approaches provide only modest symptomatic relief. In this study, we evaluated the neuroprotective effect of quercetin (25 mg/kg) administration via i.p. injection every 48 h for 3 months on aged (21-24 months old) triple transgenic AD model (3xTg-AD) mice. Our data show that quercetin decreases extracellular ß-amyloidosis, tauopathy, astrogliosis and microgliosis in the hippocampus and the amygdala. These results were supported by a significant reduction in the paired helical filament (PHF), ß-amyloid (ßA) 1-40 and ßA 1-42 levels and a decrease in BACE1-mediated cleavage of APP (into CTFß). Additionally, quercetin induced improved performance on learning and spatial memory tasks and greater risk assessment behavior based on the elevated plus maze test. Together, these findings suggest that quercetin reverses histological hallmarks of AD and protects cognitive and emotional function in aged 3xTg-AD mice.
