title: Polymorphism in the corticotropin-releasing factor receptor 1 (CRF1-R) gene plays a role in shaping the high anxious phenotype of Marchigian Sardinian alcohol-preferring (msP) rats.
abstract: BACKGROUND
  Marchigian Sardinian alcohol-preferring (msP) rats exhibit innate preference for alcohol along with anxious phenotype. In these animals, two single-nucleotide polymorphisms in position -1,836 and -2,097 from the first start codon of the CRF1-R transcript have been found.
  
  
  METHODS
  Here, we examined whether these point mutations account for the heightened anxiety-like behavior and stress responsiveness of msP rats. We rederived the msP rats to obtain two distinct lines carrying the wild-type (GG) and point mutations (AA), respectively.
  
  
  RESULTS
  CRF1-R gene expression analysis revealed significant dysregulation of the system in the extended amygdala of AA rats. At the behavioral level, using the elevated plus maze, we found that both AA and GG lines had higher basal anxiety compared to Wistar rats. In the defensive burying test, AA rats showed decreased burying behavior compared to the GG and the unselected Wistar lines. Freezing/immobility did not differ among AA and GG but was higher than that of Wistars. The selective CRF1-R antagonist antalarmin (0, 10, and 20 mg/kg) reduced burying behavior in Wistar animals. However, antalarmin (10 mg/kg) tended to increase rather than reducing this behavior when tested in the msP lines, an effect that appeared more marked in the GG as compared to the AA line.
  
  
  CONCLUSIONS
  The present data suggest that rats with msP genetic background are more anxious and show different sensitivity to stress and CRF1-R blockade than Wistars. The point mutations occurring in the CRF1-R gene do not seem to influence basal anxiety while they appear to affect active responses to stress.
authors.affiliation: Pharmacology Unit, School of Pharmacy, University of Camerino, Building of Experimental Medicine, Via Madonna delle Carceri, Camerino, MC, 62032, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cippitelli
authors.forename: Lydia O
authors.initials: LO
authors.lastname: Ayanwuyi
authors.forename: Estelle
authors.initials: E
authors.lastname: Barbier
authors.forename: Esi
authors.initials: E
authors.lastname: Domi
authors.forename: Jose M
authors.initials: JM
authors.lastname: Lerma-Cabrera
authors.forename: Francisca
authors.initials: F
authors.lastname: Carvajal
authors.forename: Giulia
authors.initials: G
authors.lastname: Scuppa
authors.forename: Hongwu
authors.initials: H
authors.lastname: Li
authors.forename: Massimo
authors.initials: M
authors.lastname: Ubaldi
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
authors.forename: Marisa
authors.initials: M
authors.lastname: Roberto
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects / Q000502:physiology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D005838:Genotype; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics*; D000099052:CRF Receptor, Type 1
chemical_list: D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D000431:Ethanol; D000099052:CRF Receptor, Type 1