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Psychopharmacology (2014) 231:16271636 DOI 10.1007/s00213-013-3353-9
ORIGINAL INVESTIGATION
Decreased prefrontal cortex dopamine activity following adolescent social defeat in male rats: role of dopamine D2 receptors
Michael J. Watt & Christina L. Roberts & Jamie L. Scholl &
Danielle L. Meyer & Leah C. Miiller & Jeffrey L. Barr &
Andrew M. Novick & Kenneth J. Renner & Gina L. Forster
Received: 1 June 2013 /Accepted: 26 October 2013 /Published online: 23 November 2013 # Springer-Verlag Berlin Heidelberg 2013
AbstractRationale 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 D2 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 intramPFC infusions of the D2 receptor agonist quinpirole, while another adolescent group received intra-mPFC infusions of the D2 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 D2 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 D2 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 D2 autoreceptors.
Keywords Adolescence . Stress . Social defeat . Prefrontal cortex . Dopamine . D2 autoreceptor . Amisulpride .
Quinpirole
Introduction
The prefrontal cortex (PFC) dopamine (DA) system is crucial for mediating cognitive control processes that permit optimal performance during complex cognitive tasks, otherwise known as executive...