Disrupted Maternal Behavior in Morphine-Dependent Pregnant Rats and Anhedonia in their Offspring

Abstract

It is currently estimated that every 15 minutes an infant is born with opioid use disorder and undergoes intense early life trauma due to opioid withdrawal. Clinical research on the long-term consequences of gestational opioid exposure reports increased rates of social, conduct, and emotional disorders in these children. Here, we investigate the impact of perinatal opioid exposure (POE) on behaviors associated with anhedonia and stress in male and female Sprague Dawley rats. Young adult female rats were administered morphine via programmable, subcutaneous micro-infusion pumps before, during, and through one week post gestation. Maternal behavior was examined for fragmentation and entropy for the first two postnatal weeks; offspring were assessed for sucrose preference, social behavior, and stress responsivity. Overall, dams that received morphine across gestation displayed significantly less pup-directed behavior with increased fragmentation for nursing and higher entropy scores. In adolescence, male and female rat offspring exposed to morphine displayed reduced sucrose preference and, as adults, spent significantly less time socially interacting with familiar conspecifics. Changes in social behaviors were linked to increased activity in nondopaminergic mesolimbic reward brain regions. Although no treatment effects were observed in forced swim test performance, corticosterone levels were significantly increased in POE adult males. Together, these results suggest that perinatal morphine exposure results in anhedonic behavior, possibly due to fragmented and unpredictable maternal behavior in opioid-dependent dams. Significance StatementClinical and preclinical research has shown that early life stress can produce lifelong depression-like symptoms. Here, we show that maternal opioid use during pregnancy produces depression-like symptoms in the offspring. We also observed disrupted maternal behavior in morphine-exposed dams that is similar to the changes in maternal behavior reported following other forms of early life stress. We propose that the stress of opioid exposure and suboptimal rearing leads to reduced sucrose preference, increased stress reactivity, and social avoidance behavior in the offspring, all of which are characteristics of anhedonia.