title: Social stress-escalated intermittent alcohol drinking: modulation by CRF-R1 in the ventral tegmental area and accumbal dopamine in mice.
abstract: BACKGROUND
  Excessive alcohol (EtOH) drinking is difficult to model in animals despite the extensive human literature demonstrating that stress increases EtOH consumption.
  
  
  OBJECTIVE
  The current experiments show escalations in voluntary EtOH drinking caused by a history of social defeat stress and intermittent access to EtOH in C57BL/6J mice compared to non-stressed mice given intermittent EtOH or continuous EtOH. To explore a mechanistic link between stress and drinking, we studied the role of corticotropin-releasing factor type-1 receptors (CRF-R1) in the dopamine-rich ventral tegmental area (VTA).
  
  
  RESULTS
  Intra-VTA infusions of a CRF-R1 antagonist, CP376395, infused into the VTA dose-dependently and selectively reduced intermittent EtOH intake in stressed and non-stressed mice, but not in mice given continuous EtOH. In contrast, intra-VTA infusions of the CRF-R2 antagonist astressin2B non-specifically suppressed both EtOH and H2O drinking in the stressed group without effects in the non-stressed mice. Using in vivo microdialysis in the nucleus accumbens (NAc) shell, we observed that stressed mice drinking EtOH intermittently had elevated levels of tonic dopamine concentrations compared to non-stressed drinking mice. Also, VTA CP376395 potentiated dopamine output to the NAc only in the stressed group causing further elevations of dopamine post-infusion.
  
  
  CONCLUSIONS
  These findings illustrate a role for extrahypothalamic CRF-R1 as especially important for stress-escalated EtOH drinking beyond schedule-escalated EtOH drinking. CRF-R1 may be a mechanism for balancing the dysregulation of stress and reward in alcohol use disorders.
authors.affiliation: Psychology Department, Tufts University, 530 Boston Avenue, Medford, MA, 02155, USA.
authors.forename: Lara S
authors.initials: LS
authors.lastname: Hwa
authors.affiliation: Psychology Department, Tufts University, 530 Boston Avenue, Medford, MA, 02155, USA.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Holly
authors.affiliation: Psychology Department, Tufts University, 530 Boston Avenue, Medford, MA, 02155, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: DeBold
authors.affiliation: Psychology Department, Tufts University, 530 Boston Avenue, Medford, MA, 02155, USA. klaus.miczek@tufts.edu.|Neuroscience Department, Tufts University, Boston, MA, 02111, USA. klaus.miczek@tufts.edu.
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Miczek
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage*; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D008845:Microinjections; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D012201:Reward; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
chemical_list: D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C104416:astressin; D000431:Ethanol; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D004298:Dopamine
keywords: Alcohol; CRF-R1; CRF-R2; Dopamine; Intermittent; Microdialysis; Nucleus accumbens; Social defeat stress; Ventral tegmental area