Abstract
Early life adversity is associated with increased risk for mental and physical health problems, including substance abuse. Changes in neural development caused by early life insults could cause or complicate these conditions. Maternal separation (MS) is a model of early adversity for rodents. Clear effects of MS have been shown on behavioral flexibility in rats, but studies of effects of MS on cognition in mice have been mixed. We hypothesized that previous studies focused on adult mice may have overlooked a developmental transition point when juvenile mice exhibit greater flexibility in reversal learning. Here, using a 4-choice reversal learning task we find that early MS leads to decreased flexibility in post-weaning juvenile mice, but no significant effects in adults. In a further study of voluntary ethanol consumption, we found that adult mice that had experienced MS showed greater cumulative 20% ethanol consumption in an intermittent access paradigm compared to controls. Our data confirm that the MS paradigm can reduce cognitive flexibility in mice and may enhance risk for substance abuse. We discuss possible interpretations of these data as stress-related impairment or adaptive earlier maturation in response to an adverse environment.
Highlights
Life experiences are known to have a profound impact on brain development and behavior
We sought to investigate how early life stress might contribute to the development of addiction-related behaviors by assessing ethanol consumption using an intermittent access “drinking in the dark” paradigm that leads to binge drinking episodes in mice (Rhodes et al, 2005; Thiele and Navarro, 2014)
Similar to the adults that had undergone maternal separation for 60 min, we found no difference in the total trials to criterion in the discrimination phase [t(28) = 0.28, P = 0.78], and in the reversal phase [t(28) = 0.66, P = 0.51] between the 180 min maternal separation group and littermates tested as adults (Fig. 4a)
Summary
Life experiences are known to have a profound impact on brain development and behavior. Changes in neural circuits supporting executive function caused by early neglect or maltreatment could both cause and/or exacerbate mental and physical health conditions. Our goal here was to develop a mouse model of effects of early life adversity on executive function with a focus on the subdomain of cognitive flexibility ( called updating in the RDoc system). We sought to investigate how early life stress might contribute to the development of addiction-related behaviors by assessing ethanol consumption using an intermittent access “drinking in the dark” paradigm that leads to binge drinking episodes in mice (Rhodes et al, 2005; Thiele and Navarro, 2014). We choose to focus on mice to enable use of the wealth of tools for the study of neural circuits that are currently most developed in this species
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