Repeated social defeat stress-induced sensitization to the locomotor activating effects of d-amphetamine: Role of individual differences

Rational: In this study, we sought to examine individual differences in stress-induced behavioral sensitization to d-amphetamine after repeated social defeat stress. In an effort to understand what mechanisms underlie stress-induced sensitization to d-amphetamine, we examined striatal gene expression of the dopamine receptor D₂. Additionally, we investigated if repeated social defeat was associated with changes in dendritic spine density in the hippocampus, prefrontal cortex, and nucleus accumbens of rats that exhibit stress-induced sensitization. Methods: Male rats were classified into high responders (HR) and low responders (LR) based on their locomotor response to a novel environment. Then, rats were either handled as a control or defeated on four occasions by aggressive rats. Two weeks after the last defeat, animals were challenged with one of three doses of d-amphetamine and their locomotor activity was recorded. Results: Non-defeated HR rats exhibited higher locomotor activity in response to d-amphetamine when compared to LR non-defeated rats. Fourteen days from the last repeated social defeat, LR rats and HR rats were behaviorally identical in response to acute injections of amphetamine. Furthermore, HR non-defeated rats had less D₂ mRNA expression in the nucleus accumbens core and dorsal striatum than do LR non-defeated rats. However, after repeated social defeat, HR and LR rats had identical D ₂ mRNA expression in both the core and dorsal striatum. Finally, there were no changes in dendritic spine density in any of the brain areas examined in LR rats. Conclusion: Repeated social defeat abolishes individual differences in behavioral responses to d-amphetamine which may be due to a down-regulation of striatal dopamine D₂ receptors in LR rats.