The effects of social hierarchy on cocaine reinforcement and brain interactions in male and female monkeys

Abstract

Male and female cynomolgus monkeys living in same‐sex social groups form linear hierarchies based on outcomes of fights. Earlier work from our laboratory found that males who became dominant (DOM) had significant increases in dopamine (DA) D2 receptor availability, as measured with PET imaging. There appeared to be behavioral consequences to the increase in D2 signal – DOM monkeys self‐administered (SA) cocaine at lower rates and intakes compared to subordinates (SUB) and the effect of high‐dose cocaine on reinstatement was blunted in DOM compared to SUBs. The present study extended this work to female monkeys. After 3 months of social housing, DOM females also showed a significant (>20%) increase in D2 receptor availability. However, unlike males, DOM females were more sensitive to the reinforcing effects of cocaine, acquiring reinforcement at lower doses than SUBs. In contrast, preliminary data suggest that cocaine pretreatments elicit substantially greater reinstatement in SUB compared to DOM females. There appear to be additional sex differences as a function of social rank related to stress responsiveness and CSF metabolite levels for DA and serotonin. The present findings indicate (1) profound sex differences in the relationship between D2 availability and cocaine reinforcement and (2) a dissociation, in females, between sensitivity to cocaine SA and cocaine‐induced reinstatement. DA17763, DA10584.