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Sex differences in prenatal stress effects on cocaine pursuit in rats
Mark B Thomas1, Jill B Becker2
1Psychology Department, University of Michigan, Ann Arbor, MI, United States; Sciformix, 1500 West Park Drive, Westborough, MA, United States.
Insights
Prenatal stress (PS) in rats increases addiction-like behaviors, especially in females. This suggests maternal stress during pregnancy may heighten vulnerability to drug abuse, particularly in women.
Area of Science:
- Neuroscience
- Developmental Psychology
- Addiction Research
Background:
- Early-life disruptions, including maternal stress during gestation (prenatal stress, PS), can have lasting health impacts.
- PS in rats enhances drug reward and neurochemical effects, indicating a potential risk factor for drug abuse.
- Sex differences in drug susceptibility are known, but PS effects specifically in females are understudied.
Purpose of the Study:
- To investigate the independent and interactive effects of maternal prenatal stress and sex on cocaine self-administration and addiction-like phenotypes in rats.
- To determine if prenatal stress exacerbates sex differences in drug susceptibility over extended exposure.
Main Methods:
- Male and female rats were exposed to maternal restraint stress during the last week of gestation or no stress (controls).
- Offspring underwent seven weeks of extended cocaine self-administration.
- Addiction-like phenotypes were assessed by drug pursuit during the final week of self-administration.
Main Results:
- Females exhibited more addiction-like criteria than males, irrespective of prenatal stress.
- Rats exposed to prenatal stress showed more addiction-like criteria than non-stressed controls.
- A significant interaction between sex and prenatal stress was observed, with females with a history of PS showing disproportionately increased drug pursuit.
Conclusions:
- Sex differences in drug susceptibility persist with prolonged drug exposure.
- Prenatal stress widens the gap in drug susceptibility between sexes by more severely impacting females.
- Prenatal stress may represent a significant risk factor for drug addiction, with a greater impact on females than males.
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.
