Methamphetamine induces neurotoxicity-associated pathways and stereological changes in prefrontal cortex

Abstract

Damage to the reward brain system is regarded as a key consequence of narcotic drug abuse, including methamphetamine (METH). The Prefrontal cortex (PFC) is one of the brain areas associated with mesocortical pathway, which plays principal roles in cognitive behavior and memory function. In spite of the potential role of PFC in METH abuse, little is known about METH-induced neurotoxicity in PFC region. In this study, we examined neurotoxicity–associated molecular pathways such as inflammation, apoptosis and autophagy in PFC under the influence of METH using quantitative real time PCR (qPCR). Besides, the protein levels of brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) as markers of synaptic plasticity and gliosis were inspected, respectively. Then we performed stereological analysis in METH-treated rats. Based on our findings, qPCR analysis revealed impaired autophagy, increased apoptosis and inflammation along with histological alterations in PFC, augmented astrogliosis as well as a significant reduction in the level of BDNF. Collectively, our molecular and histological data imply that METH administration in PFC region provoked differential expression changes in neurotoxicity-associated signaling cascades namely inflammation, apoptosis and autophagy coupled with significant PFC atrophy.