Adolescent social defeat alters neural, endocrine and behavioral responses to amphetamine in adult male rats

The mesocorticolimbic dopamine system, which governs components of reward and goal-directed behaviors, undergoes final maturation during adolescence. Adolescent social stress contributes to adult behavioral dysfunction and is linked to adult psychiatric and addiction disorders. Here, behavioral, corticosterone and limbic dopamine responses to amphetamine were examined in adult male rats previously exposed to repeated social defeat stress during mid-adolescence. Amphetamine (2.5 mg/kg, ip) was administered after a novel environment test, with behavior observed in the same context for 90 min thereafter. Adult rats that had been defeated in adolescence showed increased locomotion in the novel environment but reduced amphetamine-induced locomotion relative to non-defeated age matched controls. Monoamine and corticosterone responses to amphetamine were examined following a second amphetamine injection 3 days later. In previously defeated rats, corticosterone and medial prefrontal cortex dopamine responses to amphetamine were blunted while dopamine responses in the nucleus accumbens core were elevated. Our results suggest that experience of social defeat stress during adolescent development can contribute to altered behavioral and endocrine responses to amphetamine in adulthood. Furthermore, these effects are paralleled by changes in amphetamine-induced dopamine responses in corticolimbic systems implicated in addiction disorders.

Research Highlights
► Adolescent social defeat alters adult behavior and limbic dopamine (DA).
► Defeated rats have increased locomotion to novel environments in adulthood.
► Adolescent defeat causes decreased adult amphetamine-induced locomotion.
► Adult prefrontal cortex DA responses to amphetamine are blunted by adolescent defeat.
► Nucleus accumbens DA responses to amphetamine are elevated by adolescent defeat.