Decreased prefrontal cortex dopamine activity following adolescent social defeat in male rats: role of dopamine D sub(2) receptors

Rationale: Adverse social experience in adolescence causes reduced medial prefrontal cortex (mPFC) dopamine (DA) and associated behavioral deficits in early adulthood. Objective: This study aims to determine whether mPFC DA hypofunction following social stress is specific to adolescent experience and if this results from stress-induced DA D sub(2) receptor activation. Materials and methods: Male rats exposed to repeated social defeat during adolescence or adulthood had mPFC DA activity sampled 17 days later. Separate experiments used freely moving microdialysis to measure mPFC DA release in response to adolescent defeat exposure. At P40, 49 and 56 mPFC DA turnover was assessed to identify when DA activity decreased in relation to the adolescent defeat experience. Finally, nondefeated adolescent rats received repeated intra-mPFC infusions of the D sub(2) receptor agonist quinpirole, while another adolescent group received intra-mPFC infusions of the D sub(2) antagonist amisulpride before defeat exposure. Results: Long-term decreases or increases in mPFC DA turnover were observed following adolescent or adult defeat, respectively. Adolescent defeat exposure elicits sustained increases in mPFC DA release, and DA turnover remains elevated beyond the stress experience before declining to levels below normal at P56. Activation of mPFC D sub(2) receptors in nondefeated adolescents decreases DA activity in a similar manner to that caused by adolescent defeat, while defeat-induced reductions in mPFC DA activity are prevented by D sub(2) receptor blockade. Conclusions: Both the developing and mature PFC DA systems are vulnerable to social stress, but only adolescent defeat causes DA hypofunction. This appears to result in part from stress-induced activation of mPFC D sub(2) autoreceptors.