Cocaine self-administration in adult female and male rhesus monkeys: longitudinal comparison with adolescent behavior and role of early life stress

Year: 2025

Type: article

Abstract: A phenomenon involving cocaine use disorders is the "incubation of drug craving" - the drive for the drug increases the longer the abstinence period. The present longitudinal study provided a unique opportunity to test whether an increase in the reinforcing effects of cocaine developed after prolonged abstinence and if early life stress was a risk factor. Fourteen (N = 6 female, 8 male) adult rhesus monkeys, some (N = 7) that were maltreated as infants by their mothers (MALT), had previously self-administered cocaine under a fixed-ratio (FR) schedule of reinforcement as adolescents, but had not been studied for >3 years. In Experiment 1, cocaine self-administration dose-response curves were redetermined in adulthood when responding was maintained under the identical FR 20 schedule used during adolescence. In Experiment 2, the reinforcing strength of cocaine was evaluated (n = 12) under a progressive-ratio (PR) schedule of reinforcement. While there were no statistical differences between male and female monkeys on FR responding in adolescents, when redetermined as adults, MALT monkeys showed higher peak response rates relative to adolescence. No such differences were noted in Control monkeys. Under the PR schedule, peak reinforcing strength was not different between groups or sexes. However, higher total adolescent cocaine intake was significantly associated with higher cocaine breakpoints in adulthood. These findings show that after adolescent cocaine self-administration and a long abstinence period, sensitivity to cocaine reinforcement increased, particularly in monkeys who experienced early life stress. Although early life stress (MALT) did not significantly impact measures of cocaine's reinforcing strength, higher adolescent cocaine intake did.

Source: Neuropsychopharmacology

DOI: 10.1038/s41386-025-02161-9

Authors: Mia I. Allen, Erin R. Siebert, Alison G. P. Wakeford, Kendra Jenkins, Jessica Khan, Leonard L. Howell, Mar M. Sanchez, Michael A. Nader

Institutions: Atrium Health Wake Forest Baptist, Wake Forest University, Emory University, Emory National Primate Research Center, Wake Forest University Health Sciences

Language: English

Topic: Neurotransmitter Receptor Influence on Behavior

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,290

Funders: U.S. Department of Health and Human Services, Emory University, National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, Office of Research Infrastructure Programs, National Institutes of Health

OpenAlex ID: W4412050442