The rat corticosterone response: habituation and modification by chlordiazepoxide

Area of Science:

• Neuroscience
• Pharmacology
• Stress Physiology

Background:

• Plasma corticosterone is a key biomarker for stress responses in rodents.
• Novelty and restraint are established stressors that elevate corticosterone levels.
• Chlordiazepoxide is a benzodiazepine anxiolytic with potential stress-modulating effects.

Purpose of the Study:

• To investigate the effects of chlordiazepoxide on the rat plasma corticosterone response.
• To examine chlordiazepoxide's efficacy in novel situations and during stress (cold and restraint).
• To assess the impact of acute and repeated chlordiazepoxide administration on corticosterone levels.

Main Methods:

• Rats were exposed to three distinct novel situations, with varying degrees of behavioral control over stimulus sampling.
• Plasma corticosterone levels were measured following acute and repeated (5 and 10 days) chlordiazepoxide administration.
• Stressors included novelty, cold exposure, and restraint; chlordiazepoxide doses ranged from 5 to 50 mg/kg.

Main Results:

• All novel situations significantly increased plasma corticosterone, which decreased with repeated exposures.
• Acute chlordiazepoxide (5 mg/kg) reduced corticosterone response to novelty; pretreatment enhanced this effect.
• Chlordiazepoxide (10-50 mg/kg) reduced corticosterone response to cold and restraint stress, with tolerance developing after 10 days of treatment in most tests.

Conclusions:

• Chlordiazepoxide administration effectively attenuates plasma corticosterone elevation induced by novelty and acute stressors in rats.
• Repeated chlordiazepoxide treatment leads to the development of tolerance to its corticosterone-blocking effects.
• These findings highlight chlordiazepoxide's potential as a stress-reducer but indicate limitations due to tolerance.