Sex-specific susceptibility to cocaine in rats with a history of prenatal stress

Across species, maternal stress during prenatal life (prenatal stress [PS]) increases the expression of health complications in the developing offspring. While numerous reports indicate that male rats with a history of PS are vulnerable to psychiatric disease-like symptoms and drugs of abuse, comparable studies with females have been more limited. Here, the effects of PS in male and female rats were compared with the use of two well-validated tests of drug abuse susceptibility — the acquisition of cocaine self-administration and the expression of sensitization to the drug's psychomotor-activating properties. When a low dose (0.2 mg/kg/infusion) was available for self-administration across 15 1-hour test sessions, drug-taking behaviors were unaffected by an individual's early-life stress history. On an escalating-doses regimen (0.3–0.5 mg/kg/infusion) of self-administration, however, exposure to PS selectively facilitated the rate of acquisition and overall drug intake of males. Conversely, cocaine-induced psychomotor sensitization was augmented by PS in females, but not males. We conclude that exposure to PS enhances the reinforcing and psychomotor-sensitizing properties of cocaine male and female rats, respectively, later in life. Thus, these results suggest that gestational stress is a sex-specific risk factor for different aspects of substance abuse.