Influence of Hormones on Social Rank and Vulnerability to Cocaine Reinforcement in Female Cynomolgus Monkeys

Abstract

Nonhuman primate (NHP) social groups, which represent a continuum from environmental enrichment in dominant (DOM) monkeys to chronic social stress in subordinates (SUB), have been used to study susceptibility and resilience to human diseases, including drug abuse. We have shown that social rank influences sensitivity to cocaine (COC) in NHPs, although it is not clear how hormone fluctuations may influence rank or how hormones are modified after rank is established. This study used female NHPs and examined whether estrogen (E2), progesterone (P4) or testosterone (T) predicted eventual rank, changed following hierarchy establishment, or was associated with susceptibility to COC self‐administration (SA). Prior to social housing, E2 exposure across the menstrual cycle was greater in eventual SUB compared to eventual DOM; there were no differences in P4. After hierarchies were formed (4 monkeys/pen), E2 exposure across the cycle decreased in SUB and differences between ranks were no longer observed. DOM had decreases in P4 after hierarchies stabilized, whereas SUB showed increases in P4 following rank formation. T concentrations did not predict or differ between ranks; decreases in T concentrations were observed across all ranks following hierarchy formation. When given access to COC (0.0003‐0.1 mg/kg/inj), SUB acquired COC SA at lower doses than DOM. This effect could be driven by higher circulating E2 since an inverse relation between E2 and dose of COC at which SA occurred was observed. These results enhance our understanding of an individual's response to factors related to social environment and their relationship to COC SA. Such information will aid in the development of pharmacological treatment strategies for drug addiction. DA017763, DA036973