title: A lack of tolerance to the anxiolytic effects of diazepam on the plus-maze: comparison of male and female rats.
abstract: BACKGROUND
  The demonstration of tolerance to the anxiolytic effects of benzodiazepines remains inconsistent.
  
  
  OBJECTIVE
  The present study tested the hypothesis that intact and gonadectomized male and female rats might exhibit differential tolerance to the anxiolytic effects of diazepam (DZ).
  
  
  METHODS
  Following acute (3 days) or chronic (3 weeks) DZ exposure, all animals were tested on the elevated plus-maze and immediately sacrificed for analysis of corticosterone, adrenocorticotropin hormone, estrogen and progesterone levels in serum. In experiment 2, following acute or chronic DZ exposure, animals were treated with a DZ challenge dose on the test day.
  
  
  RESULTS
  In experiment 1, both acute and chronic DZ treatment similarly enhanced percentage open arm time and entries, regardless of the hormonal status of the animal. The results of experiment 2 showed that both acute and chronic DZ-treated animals exhibited a significantly higher percentage open arm time than control animals after the DZ challenge dose, and males and females did not differ in their responses to DZ exposure.
  
  
  CONCLUSIONS
  The findings from these experiments suggest that tolerance to the anxiolytic effects of DZ did not develop in males or females, and that the hormonal status of the animal does not significantly alter the anxiolytic effects of DZ following either acute or chronic exposure. Following plus-maze exposure, females had significantly higher corticosterone levels than males and acute DZ treatment diminished this stress response.
authors.affiliation: University of South Carolina, School of Medicine, Department of Pharmacology, Columbia 29208, USA. hstock@dcsmserver.med.sc.edu
authors.forename: H
authors.initials: H
authors.lastname: Stock
authors.forename: C
authors.initials: C
authors.lastname: Foradori
authors.forename: K
authors.initials: K
authors.lastname: Ford
authors.forename: M A
authors.initials: MA
authors.lastname: Wilson
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000097:blood / Q000523:psychology*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004958:Estradiol / Q000097:blood; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D011869:Radioligand Assay; D051381:Rats; D020318:Rats, Long-Evans; D012727:Sex Characteristics
chemical_list: D014151:Anti-Anxiety Agents; D011374:Progesterone; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D003975:Diazepam; D006854:Hydrocortisone