Neurotoxic Assessment of Chronic Abuse of Pregabalin in Wistar Rats

Abstract

Pregabalin (Lyrica) is an analog of the gamma-aminobutyric acid neurotransmitter,   approved for the treatment of epilepsy, generalized anxiety disorder, neuropathic pain, and fibromyalgia. The possibility for abuse and/or dependence on pregabalin has risen recently. Pregabalin is controlled in many countries including Saudi Arabia. However, unofficial use of this substance is also on the increase. The purpose of this study is to assess the potential neurotoxic effects associated with overdose prolonged pregabalin supplementation. Forty male Wistar rats were divided into Group (1) normal control received distilled water, Group (2) received pregabalin (150mg/kg), Group (3) received pregabalin (300 mg/kg), and Group (4) received pregabalin (600 mg/kg). pregabalin consumption in different doses resulted in significant dysregulation in neurotransmitter release, upsurge oxidative stress markers via enhancing lipid peroxidation and depleting antioxidant markers. Also, pregabalin doses evoked brain tissue inflammation through elevating TNF-α, IL-1β, and MCP-1, Moreover promoted brain tissue apoptosis by activating caspase -3 and suppressed Bcl2. Pregabalin effects on the aforementioned parameters were dose-dependent. These findings could highlight the potential neurotoxic effect of prolonged abuse of pregabalin supplementation through dysregulating brain neurochemical, inflammatory, oxidant/antioxidant, and apoptotic mediators.