Examining Early Life Stress as a Vulnerability Trait in Cocaine Self‐Administration in Rhesus Macaques
Authors: Wakeford Alison , Bramlett Sara N , Sanchez Mar M , Howell Leonard L 
Published: November 2023

Early life stress (ELS) is one of the most reliable and predictive factors for the emergence of psychopathologies in adolescence, including addiction. While ELS can be defined in many ways, maternal abuse and neglect constitutes an extreme form of ELS that has debilitating consequences to the infant. As a result of this abuse and neglect, the infant displays stressful behaviors that persist into adolescence that are corroborated by hormonal as well as some possible neurobiological changes. Nonhuman primates, specifically rhesus monkeys, show a similar distribution of maternal care as humans, in that some mothers show maternal abuse and neglect towards their infants. The prevalence of this abuse is similar in captivity as it is in the wild, and provides researchers a unique opportunity to study an organic model of ELS that is not experimenter induced.

Accordingly, we examined whether rhesus monkeys maltreated early in life (MALT; n = 7) show a greater vulnerability to cocaine self‐administration (SA) in comparison to control monkeys (Control; n = 2). Animals were trained to respond under a fixed‐ratio 20 response (FR 20) schedule of reinforcement, where upon completion of the FR resulted in an infusion of cocaine (0.01–0.1 mg/kg/infusion). After meeting criteria for stable self‐administration, animals progressed through a full dose‐effect curve to establish the dose that engendered the highest response rate while allowing animals to receive all possible infusions (maximum of 20). Rate of acquisition, cocaine consumption, sensitivity to and magnitude of the reinforcing effects of cocaine were examined in both groups.

There were no differences in rate of acquisition between MALT and control animals. MALT animals consumed less cocaine (mg/kg/infusion) in comparison to Control animals. Similarly, MALT animals showed an increased sensitivity to the reinforcing effects of cocaine, such that the dose used to engender stable self‐administration was markedly lower than Control animals. MALT animals showed a greater magnitude of reinforcing effects of cocaine, demonstrated by a greater response rate (responses/sec) than Control animals.

These preliminary data suggest that animals maltreated early in life show an enhanced vulnerability to the reinforcing effects of cocaine. Future experiments will include examining drug‐ and cue‐induced reinstatement in animals with ELS, given that humans who have experienced ELS show a heightened predisposition towards emotional dysregulation which may lead to stress‐induced relapse. Furthermore, as subjects are added to these ongoing studies, sex will be studied as a major factor in all experimental endpoints, given that women show a higher prevalence of anxiety as well as a greater susceptibility in progressing from drug experimentation to drug dependence.

Support or Funding Information

This research was supported by USPHS grants DA 038588 (MMS/LLH), DA 010344 (LLH), DA 031246 (LLH), and P51OD11132 (Yerkes National Primate Research Center).