Regulation of Adult Neurogenesis by Methamphetamine

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DESCRIPTION (provided by applicant): My immediate goal is to establish myself as an independent researcher in the fields of neuroscience and cell biology, and obtain training in methods such as drug self-administration and animal behavior. For my long- term goals, I see myself as a faculty member in an academic environment with an established independent laboratory focusing on neuroscience and pursuing my interests in drug abuse and adult neurogenesis. Abuse of the psychostimulant methamphetamine has reached epidemic proportions and poses significant medical and social problems in the United States. Methamphetamine abuse in humans severely damages the prefrontal cortex and hippocampus, reducing cortical and hippocampal volume and producing memory deficits. Interestingly, adult precursor cell genesis has been demonstrated in the proliferative regions of the mammalian brain, namely, the medial prefrontal cortex (mPFC) and the hippocampal subgranular zone (SGZ). The newly born precursors mature into neurons or glia and are implicated in maintaining adult brain structure and function. While the devastating effects of methamphetamine on the structure and function of the RFC and hippocampus are becoming very clear, very little information exists on the affects of methamphetamine on adult gliogenesis and neurogenesis. The objective of this proposal is to investigate the mechanisms underlying methamphetamine self-administration-induced decrease in cell proliferation, gliogenesis and neurogenesis in the adult rat mPFC and hippocampus and to explore a possible relationship between methamphetmine-induced alterations in cortical and hippocampal structure and function. Importantly, we will use a clinically relevant self-administration paradigm of methamphetamine exposure to implement our specific aims. First, we will determine the harmful effects of methamphetamine escalation on cell proliferation and cell death over an escalation time course. Second, we will explore a possible mechanism for chronic methamphetamine-induced decrease in adult cortical and hippocampal gliogenesis and neurogenesis. Third, we will uncover the relationship between chronic methamphetamine- induced alteration in cell genesis and behavior. Taken together, our findings will improve our understanding of the complex mechanisms by which chronic exposure to psychostimulants affect adult brain function and may help generate better therapies to treat methamphetamine addiction.