Repeated benzodiazepines ingestions affected behavioral and neurochemical profiles, with mild effect on histological integrities: modulatory efficacy of Nigella sativa oil

Abstract

Background: Benzodiazepines (BZDs) are a class of depressant drugs that have enjoyed widespread use in conventional clinical management of anxiety-related conditions such as panic disorders that require therapeutic central relaxation and sedation. Meanwhile, prolonged administration of benzodiazepines even at low doses has however been linked to variety of undesirable effects such as discontinuation relapse with the associated risk of abuse and dependency. Aim: This study investigated the behavioral, histological and biochemical outcomes of long-term low dose diazepam use and explored the potential role of nigella sativa oil (NSO) in the amelioration of the associated side effects. Methods: Adult Wistar rats (n=32) were randomized into four groups that received normal saline; diazepam; diazepam + NSO; or NSO only, respectively for 14 days. At the end of the period of the various exposures, the rats were taken through behavioral paradigms after which they were sacrificed for chemical and histological profiling. Results: diazepam-exposed rats exhibited stress-related manifestations with relatively poor performance in memory-related tasks. Repeated diazepam ingestion reduced brain antioxidant biomarkers while causing elevation of brain oxidative stress markers. On histological observation, mild degenerative changes were evident in the various brain regions of the diazepam-exposed rats. Conclusion: Interventional nigella sativa oil administration showed therapeutic potentials by mitigating and reversing the observed effects of diazepam, largely due to its antioxidant and anti-inflammatory effects as observed in the present study.