Alleviation of diazepam-induced conditioned place preference and its withdrawal-associated neurobehavioral deficits following pre-exposure to enriched environment in rats

Diazepam is one of the widely prescribed sedative drugs for the treatment of anxiety and sleep disorders. However, its continuous use can induce addiction, tolerance, and withdrawal symptoms and, therefore, the pharmacological use of diazepam is restricted. Exposure to enriched environment can reduce the addiction to stimulants including amphetamine, cocaine, and nicotine. However, the protective effect of enriched environment against preference of sedative drugs is not yet investigated. This study, therefore, determined the effects of enriched environment to prevent diazepam-preference using conditioned place preference (CPP) paradigm. Adult rats were reared in social (n = 12) or physically (n = 12) enriched environment for four weeks. Each group was then sub-divided into two groups and were administered either saline (Control; n = 6) or diazepam (1 mg/kg; n = 6) on alternate days for thirteen days. During the administration of diazepam, the CPP was conducted to monitor drug preference on 5th, 9th and 13th day of experiment. It was observed that the diazepam administration significantly (p <.01) induced preference in rats. Neurobehavioral deficits including hypolocomotor activity, depression-like behavior, impaired learning and memory functions were also observed after 24 h of drug abstinence. Exposure to enriched environment significantly reduced diazepam-preference and other neurobehavioral deficits. This study provides preliminary evidence to highlight the importance of enriched environment in the attenuation of diazepam-preference.