Morphine exposure alters Fos expression in a sex-, age-, and brain region-specific manner during adolescence

Data in both humans and preclinical animal models clearly indicate drug exposure during adolescence, when the "reward" circuitry of the brain develops, increases the risk of substance use and other mental health disorders later in life. Human data indicate that different neural and behavioral sequelae can be observed in early versus late adolescence. However, most studies with rodent models examine a single adolescent age compared to a mature adult age, and often only in males. Herein, we sought to determine whether the acute response to the opioid morphine would also differ across adolescence, and by sex. By quantifying Fos positive cells, a proxy for neural activity, at different stages during adolescence (pre-, early, mid-, and late adolescence) and in multiple reward regions (prefrontal cortex, nucleus accumbens, caudate/putamen), we determined that the neural response to acute morphine is highly dependent on adolescent age, sex, and brain region. These data suggest that heterogeneity in the consequences of adolescent opioid exposure may be due to age- and sex-specific developmental profiles in individual reward processing regions. In future studies, it will be important to add age within adolescence as an independent variable for a holistic view of healthy or abnormal reward-related neural development.