Morphine exposure during adolescence induces enduring social changes dependent on adolescent stage of exposure, sex, and social test.

Abstract

Drug exposure during adolescence, when the “reward” circuitry of the brain is developing, can permanently impact reward-related behavior into adulthood. Epidemiological studies show that opioid treatment during adolescence, such as pain management for a dental procedure or surgery, increases the incidence of psychiatric illness including substance use disorders. Moreover, the opioid epidemic currently in the United States is affecting younger individuals raising the impetus to understand the pathogenesis of the negative effects of opioids. One reward-related behavior that develops during adolescence is social behavior. We previously demonstrated that developmental changes in the nucleus accumbens reward region regulate social development in rats during sex-specific adolescent periods: early to mid-adolescence in males (postnatal day, P30–40) and preearly adolescence in females (P20–30). We thus hypothesized that the developmental stage of morphine exposure will differentially impact social behavior development such that drug administered during the female critical period would result in adult sociability deficits in females, but not males, and morphine administered during the male critical period would result in adult sociability deficits in males, but not females. We found that morphine exposure during the female critical period primarily resulted in deficits in sociability in females, while morphine exposure during the male critical period primarily resulted in deficits in sociability primarily in males. However, depending on the test performed and the social parameter measured, social alterations could be found in both sexes that received morphine exposure at either adolescent stage. These data indicate that when drug exposure occurs during adolescence, and how the endpoint data are measured, will play a large role in determining the effects of drug exposures on social development.