Abstract
Disruption of early-life ontogeny has severe and persistent consequences for the health of the developing organism. Both clinical and preclinical findings indicate that such interference can be caused by maternal stress during the gestation period (prenatal stress [PS]). In rats, PS facilitates the rewarding and neurochemical-stimulating effects of drugs, suggesting that PS may represent a risk factor for drug abuse in humans. Very little, however, is known about its effects in females, even though sex differences in drug susceptibility have been well documented in no PS (NPS) controls. Thus, we tested for independent effects and interactions between maternal restraint stress during the last week of gestation and sex on drug use with an extended regimen of drug self-administration. Male and female rats were provided daily access to a large but controlled amount of cocaine for seven weeks. Drug pursuit during the final week was used to indicate susceptibility to developing an addiction-like phenotype, based on reports that drug use becomes increasingly compulsive-like after weeks of testing. Overall, females satisfied more addiction-like criteria than males, and the same was true for PS rats when compared to NPS controls. In addition, sex and PS interacted to disproportionately promote drug pursuit of females with a history of PS. These results indicate that sex differences in drug susceptibility persist with continued drug exposure, and that PS widens this difference by more severely affecting females. In all, PS may be a risk factor for drug addiction in humans, and to a greater extent in women vs. men.