title: Corticotropin-releasing factor antagonist attenuates the "anxiogenic-like" effect in the defensive burying paradigm but not in the elevated plus-maze following chronic cocaine in rats.
abstract: BACKGROUND
  Chronic cocaine abuse is associated with the development of anxiogenic states in humans. Corticotropin-releasing factor (CRF) is an endogenous neurotropic factor well known to modulate stress responses. It has been postulated that CRF is involved in the neurobiological mechanisms underlying the anxiety and/or stress responses associated with removal of cocaine after chronic administration.
  
  
  OBJECTIVE
  The present study investigated the role of endogenous CRF in mediating the "anxiety-like" effect 48 h after the cessation of saline or chronic cocaine treatment in rats, using the defensive burying paradigm and the elevated plus-maze.
  
  
  METHODS
  Rats received daily injections of cocaine (20 mg/kg IP, for 14 consecutive days) or vehicle. Forty-eight hours after the last injection, animals were tested in the plus-maze and then in the defensive burying paradigm. In a second experiment, intracerebroventricular (ICV) cannulae were implanted at the lateral ventricle. Animals were allowed a 1-week period for recovery before starting the chronic drug treatment. The defensive burying testing took place 48 h after cessation of the treatment. The CRF antagonist [DPhe12, Nle21,38, CalphaMe Leu37] r/h CRF(12-41), (also known as D-phe CRF(12-41)) (0.04, 0.2 and 1.0 microg/5 microl) was injected 5 min before the 15-min testing.
  
  
  RESULTS
  An "anxiogenic-like" effect following chronic cocaine treatment was demonstrated with the defensive burying paradigm, but not with the elevated plus-maze. This "anxiety-like" response was attenuated by ICV pretreatment with the CRF antagonist D-Phe CRF(12-41), with the highest dose of the CRF antagonist reversing the observed "anxiogenic-like" response.
  
  
  CONCLUSIONS
  These data suggest that brain CRF may be substantially involved in the development of "anxiety-like" responses related to cocaine withdrawal and could be important for future drug dependence treatments.
authors.affiliation: Department of Neuropharmacology CVN-7, La Jolla, CA 92037, USA. ambasso@fcq.unc.edu.ar
authors.forename: A M
authors.initials: AM
authors.lastname: Basso
authors.forename: M
authors.initials: M
authors.lastname: Spina
authors.forename: J
authors.initials: J
authors.lastname: Rivier
authors.forename: W
authors.initials: W
authors.lastname: Vale
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000009:adverse effects*; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D013287:Illicit Drugs / Q000009:adverse effects*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
chemical_list: D014151:Anti-Anxiety Agents; C083591:H-R corticotropin-releasing factor (12-41), Phe(12)-Nle(21,38), C(alpha-MeLeu(37))-; D013287:Illicit Drugs; D010446:Peptide Fragments; C113202:phenylalanyl corticotropin-releasing factor (12-41); D003346:Corticotropin-Releasing Hormone; D003042:Cocaine