Gabapentin: a newly emerging drug of abuse, neurotoxicity, and potential addictive mechanisms

Abstract

Background

Following the scheduling of pregabalin, gabapentin (GBP) misuse and abuse had been escalated in Egypt over the past ten years. Pregabalin negative effects had been shown in numerous studies; however those of GBP are negligible. The goal of this research is studying and assessing the neurotoxic and potential addictive mechanisms of subchronic high doses of GBP.

Methods

Thirty (30) adult healthy male albino rats were randomly divided into three groups (10 rats each): group I with normal diet as a negative control, group II GBP misuse, group III GBP withdrawal. All rats were given GBP for 50 days. Then group III rats were maintained for an additional 10 days without GBP. On the day of scarification, animal neurobehavioral tests were conducted. Hippocampal samples were obtained for histopathological, immune-histochemical examination and measurement of gene expression of brain-derived neurotrophic factor (BDNF) and dopamine receptors.

Results

By the end of the study, the weight gain of the drug treated groups had significantly increased (P < 0.001). Controls had better performance and locomotor indices in neurobehavioral tests. GBP misuse group had greater detrimental effects on hippocampal tissues and increased numbers of degenerated cells. These histopathological changes significantly declined after GBP withdrawal period. Up-regulation of dopamine-2 receptors (D2Rs) (P < 0.005) and down regulation of dopamine-1 receptors (D1Rs) (P < 0.01) were more evident in GBP misuse group than withdrawal group whereas BDNF gene expression was up-regulated in both groups (P < 0.556).

Conclusions

High dose subchronic administration of GBP was associated with numerous histopathological changes that were declined during withdrawal period. The relatively low expression of (D1Rs) to (D2Rs) suggested the GBP potential of abuse and the recreational misuse among individuals with substance use disorder.