Effects of early life stress on cocaine self-administration in post-pubertal male and female rhesus macaques

• Published in: Psychopharmacology 2019-09, Vol.236 (9), p.2785-2796
• Main Authors: Wakeford, Alison G. P., Morin, Elyse L., Bramlett, Sara N., Howell, Brittany R., McCormack, Kai M., Meyer, Jerrold S., Nader, Michael A., Sanchez, Mar M., Howell, Leonard L.
• Format: Article
• Language: English
• Subjects: Adolescents; Analysis; Animal behavior; Animals; Behavior; Biomedical and Life Sciences; Biomedicine; Catheters; Children; Cocaine; Dosage and administration; Drug self-administration; Females; Gender differences; Intravenous administration; Males; Monkeys; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Psychological aspects; Response rates; Rhesus monkey; Schedules; Sensitivity; Sex differences; Stress (Psychology)
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-019-05254-8

Rationale Early life stress (ELS), including childhood maltreatment, is a predictive factor for the emergence of cocaine use disorders (CUDs) in adolescence. Objective Accordingly, we examined whether post-pubertal male and female rhesus macaques that experienced infant maltreatment (maltreated, n  = 7) showed greater vulnerability to cocaine self-administration in comparison with controls (controls, n  = 7). Methods Infant emotional reactivity was measured to assess differences in behavioral distress between maltreated and control animals as a result of early life caregiving. Animals were then surgically implanted with indwelling intravenous catheters and trained to self-administer cocaine (0.001–0.3 mg/kg/infusion) under fixed-ratio schedules of reinforcement. Days to acquisition, and sensitivity to (measured by the ED Max dose of cocaine) and magnitude (measured by response rates) of the reinforcing effects of cocaine were examined in both groups. Results Maltreated animals demonstrated significantly higher rates of distress (e.g., screams) in comparison with control animals. When given access to cocaine, control males required significantly more days to progress through terminal performance criteria compared with females and acquired cocaine self-administration slower than the other three experimental groups. The dose that resulted in peak response rates did not differ between groups or sex. Under 5-week, limited-access conditions, males from both groups had significantly higher rates of responding compared with females. Conclusions In control monkeys, these data support sex differences in cocaine self-administration, with females being more sensitive than males. These findings also suggest that ELS may confer enhanced sensitivity to the reinforcing effects of cocaine, especially in males.