Early life stress alters opioid receptor mRNA levels within the nucleus accumbens in a sex-dependent manner

Abstract

Early life stress (ELS) strongly impacts mental health, but little is known about its interaction with biological sex and postnatal development to influence risk and resilience to psychopathologies. A number of psychiatric disorders, such as social anhedonia and drug addiction, involve dysfunctional opioid signaling; moreover, there is evidence for differential central opioid function in males vs. females. The present study examined opioid receptor gene expression in the nucleus accumbens (NAc) and amygdala of male and female rats subjected to a neonatal predator odor exposure (POE) paradigm to model ELS. Brain tissue was collected at two developmental time points: neonatal and juvenile. Results showed that, following the neonatal POE experience, opioid receptor mRNA levels in the NAc were differentially regulated at the neonatal and juvenile time points. POE downregulated neonatal mu- and kappa-opioid receptor mRNA levels in neonatal females, but upregulated mu- and delta-opioid receptor mRNA levels in juvenile females. Intriguingly, POE had no significant effect on NAc opioid receptor mRNA levels in males at either time point, indicating that the impact of POE on opioid system development is sex-dependent. Finally, POE failed to alter amygdalar opioid receptor gene expression in either sex at either time-point. The spatiotemporally- and sex-specific impact of ELS within the developing brain may confer differential risk or resilience for males and females to develop atypical opioid-regulated behaviors associated with conditions such as depression and addiction.