In Vivo Effects of Chronic Methamphetamine Exposure: A Study of Elemental and Inflammatory Responses and Potential Mechanisms for Zinc Accumulation in the Midbrain.

Abstract

Methamphetamine (METH) is a widely used drug of abuse in the United States (NIDH 2013). The characteristic “high” associated with METH intoxication comes from the excessive release of dopamine (DA) into the neuronal synapse. The oxidative damage due to DA release is amplified by blocked reuptake of the neurotransmitter (Ajjimaporn et al., 2005; Ajjimaporn et al., 2008; Cadet et al., 1994;Mirecki, 2004). During the increased time in the synapse, DA causes irreparable damage to the neuron terminals leaving lasting effects on the brain (Cadet et al., 1994; Riddle et al., 2006). In the laboratory, the damaging effects of METH are used to model neurodegenerative disease states that affect the dopaminergic pathways. Three major dopaminergic pathways exist in the brain. The mesocortical pathway begins in the ventral tegmental area (VTA) and extends to the prefrontal cortex (PFC). The mesolimbic pathway projects from the VTA to the striatum (STR). The nigrostriatal pathway projects from the substantia nigra (SN) to the STR. Due to their close proximity, for the purpose of this thesis, the SN and VTA are paired together and collectively referred to as the midbrain (MB). Dopaminergic cell bodies reside in the MB and project their axons to the PFC and STR. Therefore, all three regions (PFC, STR, and MB) are key in studying the neurotoxic effects of METH.