Impact of brief maternal separation on rodent models of anergia induced by dopamine depletion: analysis in mice of both sexes during adulthood

Mesolimbic dopamine (DA) regulates activation and effort in motivated behaviors. Impairments in DA function induce motivational symptoms such as anergia and fatigue seen in depression. Stress modulates DA depending on its duration and intensity. Early-life events such as maternal separation (MS) could act as stressors, affecting brain development and leading to behavioral changes later in life. However, little is known about the effect of early-life stressors on adult motivational processes and effort-based decision-making. CD1 male and female mice were subjected to early-mild MS (PND3-5, 90 min/day), and, during adulthood, were evaluated on selection of effortful responses under positive or aversive experimental conditions. The choice to engage in effortful activities such as running in a wheel versus engaging with passive reinforcers was evaluated in a three-choice-T-maze task. In the forced-swim task (FST), time dedicated to vigorously escaping versus passively floating was measured. MS mice of both sexes, spent more time in the RW, and climbing in the FST, showing an increase in relative preferences for activity-based reinforcers, and persistence in vigorous escaping from aversive contexts compared to non-separated mice. Separated animals were less anxious but males were less socially oriented. In adulthood, DA depletion induced anergic patterns both in the T-maze and in the FST only in males independently of separation conditions. Measures of anxiety, social interaction and sucrose preference and consumption were not affected after DA depletion. Thus, mild-early MS promotes effortful behaviors during adulthood in both sexes independently of the emotional value of the situation, but males were more vulnerable than females to DA-depletion induced-anergia.