Abstract:
INTRODUCTION: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. MATERIALS AND 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. CONCLUSION: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.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Cippitelli A,Ayanwuyi LO,Barbier E,Domi E,Lerma-Cabrera JM,Carvajal F,Scuppa G,Li H,Ubaldi M,Heilig M,Roberto M,Ciccocioppo Rdoi
10.1007/s00213-014-3743-7subject
Has Abstractpub_date
2015-03-01 00:00:00pages
1083-93issue
6eissn
0033-3158issn
1432-2072journal_volume
232pub_type
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