Anxiety, aggression, reward sensitivity, and forebrain dopamine receptor expression in a laboratory rat model of early‐life disadvantage

Abstract

AbstractDespite early‐life disadvantage (ELD) in humans being a highly heterogenous construct, it consistently predicts negative neurobehavioral outcomes. The numerous environmental contributors and neural mechanisms underlying ELD remain unclear, though. We used a laboratory rat model to evaluate the effects of limited resources and/or heavy metal exposure on mothers and their adult male and female offspring. Dams and litters were chronically exposed to restricted (1‐cm deep) or ample (4‐cm deep) home cage bedding postpartum, with or without lead acetate (0.1%) in their drinking water from insemination through 1‐week postweaning. Restricted‐bedding mothers showed more pup‐directed behaviors and behavioral fragmentation, while lead‐exposed mothers showed more nestbuilding. Restricted bedding‐raised male offspring showed higher anxiety and aggression. Either restricted bedding or lead exposure impaired goal‐directed performance in a reinforcer devaluation task in females, whereas restricted bedding alone disrupted it in males. Lead exposure, but not limited bedding, also reduced sucrose reward sensitivity in a progressive ratio task in females. D1 and D2 receptor mRNA in the medial prefrontal cortex and nucleus accumbens (NAc) were each affected by the early‐life treatments and differently between the sexes. Most notably, adult males (but not females) exposed to both early‐life treatments had greatly increased D1 receptor mRNA in the NAc core. These results illuminate neural mechanisms through which ELD threatens neurobehavioral development and highlight forebrain dopamine as a factor.