Efectos de la exposición prenatal a cocaína en la conducta emocional en ratones

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Abstract

El objetivo de este estudio fue analizar los efectos de la Exposición Prenatal a Cocaína (EPC) (0,25 o 50 mg/kg/día) en la conducta emocional de ratones hembras y machos en la adolescencia y la adultez temprana. Se asignaron 27 ratones CD1 hembras gestantes a 3 condiciones experimentales: un grupo control que se le administró solución salina y 2 experimentales a los que se le administró cocaína 25 mg/ kg/día y 50 mg/kg/día, desde el día octavo al veintiunavo de gestación. La conducta emocional de los hijos de estas madres se evaluó en la adolescencia y en la adultez temprana (5.ª y 7.ª semana de edad, respetivamente) por medio del tablero de agujeros y el laberinto en cruz a través de diferentes índices de actividad exploratoria. Los datos se analizaron por medio de MANOVAS y ANOVAS con un valor a de 0.05. La EPC alteró de forma dosis-relacionada la conducta emocional; los sujetos sometidos a EPC 50 mg/kg/día exhibieron mayor ansiedad y temor, en cambio los tratados con EPC 25 mg/kg/día exploraron más, mostrando conductas de alto riesgo, características de la impulsividad e hiperactividad. Los efectos encontrados se mantuvieron en el tiempo, por lo que se concluye que la EPC perturbó permanente y significativamente la emoción.

Translated abstract

In order to study the effects of prenatal cocaine exposure (0, 25 or 50 mg/kg/day), on the emotional behavior of young and adult mice of both sexes, 27 CD1 pregnant female mice were assigned to one of three experimental conditions: a control group was given saline solution, a first experimental group that was given 25 mg/kg/day of cocaine and another experimental group with 50 mg/kg/day of cocaine, all between gestational days 8-21. Emotional behavior was evaluated in the offspring (both males and females) of the females at five and seven weeks of age, via the hole board followed by the plus maze with different rates of exploratory activity. Data were analyzed with MANOVAS and ANOVAS with and a of 0.05. Prenatal Cocaine Exposure (PCE) altered dose-related emotional behavior; subjects with PCE of 50 mg/kg/day exhibited more anxiety and fear, in contrast to the 25 mg/kg/day group that explored more and showed greater high-risk behaviors, which are features of impulsivity and hyperactivity. The effects found were maintained over time, so it is concluded that PCE permanently and significantly perturbed emotion.

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Programming the brain and behaviour by early-life stress: a focus on neuroactive steroids.

P J Brunton (2015)

Animal studies have amply demonstrated that stress exposure during pregnancy or in early postnatal life can adversely influence brain development and have long-term 'programming' effects on future brain function and behaviour. Furthermore, a growing body of evidence from human studies supports the hypothesis that some psychiatric disorders may have developmental origins. Here, the focus is on three adverse consequences of early-life stress: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, heightened anxiety behaviour and cognitive impairments, with review of what is known about the underlying central mechanisms. Neuroactive steroids modulate neuronal activity and play a key role in neurodevelopment. Moreover they can negatively modulate activity of the HPA axis, exert anxiolytic actions and influence cognitive performance. Thus, neuroactive steroids may provide a link between early-life stress and the resultant adverse effects on the brain and behaviour. Here, a role for neuroactive steroids, in particular the 5α-reduced/3α-hydroxylated metabolites of progesterone, testosterone and deoxycorticosterone, is discussed in the context of early-life stress. Furthermore, the impact of early-life stress on the brain's capacity to generate neurosteroids is considered and the evidence for an ability of neuroactive steroids to over-write the negative effects of early-life stress on the brain and behaviour is examined. An enhanced understanding of the influence of early-life stress on brain neurosteroid systems could aid the identification of new targets for developing treatments for stress-related conditions in humans.