H Stock1, C Foradori, K Ford, M A Wilson. 1. University of South Carolina, School of Medicine, Department of Pharmacology, Columbia 29208, USA. hstock@dcsmserver.med.sc.edu
Abstract
RATIONALE: The demonstration of tolerance to the anxiolytic effects of benzodiazepines remains inconsistent. OBJECTIVES: 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.
RATIONALE: The demonstration of tolerance to the anxiolytic effects of benzodiazepines remains inconsistent. OBJECTIVES: 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: Stefany D Primeaux; Steven P Wilson; Alexander J McDonald; Franco Mascagni; Marlene A Wilson Journal: Pharmacol Biochem Behav Date: 2006-11-15 Impact factor: 3.533
Authors: Adriaan W Bruijnzeel; Azin Behnood-Rod; Wendi Malphurs; Ranjithkumar Chellian; Robert M Caudle; Marcelo Febo; Barry Setlow; John K Neubert Journal: Behav Pharmacol Date: 2022-08-03 Impact factor: 2.277