title: Increased mesocorticolimbic dopamine during acute and repeated social defeat stress: modulation by corticotropin releasing factor receptors in the ventral tegmental area.
abstract: BACKGROUND
  Stress activates a subset of dopamine neurons in the ventral tegmental area (VTA), increasing extracellular dopamine in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (NAcSh). The stress neuropeptide corticotropin releasing factor (CRF) and its receptors (CRF-R1 and CRF-R2) are located within the VTA and directly and indirectly influence dopaminergic activity. However, it has yet to be shown in vivo whether VTA CRF receptor activation is necessary for acute and repeated stress-induced dopamine efflux.
  
  
  OBJECTIVE
  With intra-VTA CRF-R1 and CRF-R2 antagonism during social defeat, we assessed whether blockade of these receptors could prevent stress-induced dopamine increases in the mPFC and NAcSh using in vivo microdialysis.
  
  
  METHODS
  Rats were microinjected with a CRF-R1 or CRF-R2 antagonist into the VTA prior to social defeat stress on days 1, 4, 7, and 10. In vivo microdialysis for dopamine in the mPFC and NAcSh was performed during stress on days 1 and 10.
  
  
  RESULTS
  During the first social defeat, extracellular dopamine was significantly elevated in both the mPFC and NAcSh, and this increase in the NAcSh was blocked by intra-VTA CRF-R2, but not CRF-R1, antagonism. During the final social defeat, the dopaminergic increase was neither sensitized nor habituated in the mPFC and NAcSh, and intra-VTA CRF-R2, but not CRF-R1, antagonism prevented the dopamine increase in both brain regions.
  
  
  CONCLUSIONS
  These findings show that CRF-R2 in the VTA is necessary for acute and repeated stress-induced dopamine efflux in the NAcSh, but is only recruited into mPFC-projecting dopamine neurons with repeated stress exposure.
authors.affiliation: Department of Psychology, Tufts University, Medford, MA, USA. Elizabeth.Holly@tufts.edu.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Holly
authors.affiliation: Department of Psychology, Tufts University, Medford, MA, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: DeBold
authors.affiliation: Department of Psychology, Tufts University, Medford, MA, USA.|Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Miczek
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012930:Social Dominance; D013315:Stress, Psychological / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D004298:Dopamine
keywords: CRF-R1; CRF-R2; Corticotropin releasing factor; Dopamine; Social defeat; Ventral tegmental area