The primary objectives of Component 8 are to test key aspects of our unique theoretical model focused on neuroimmune mechanisms contributing to methamphetamine-induced neuropsychiatric impairments. We also test our central hypothesis that immunomodulatory agents can promote brain healing and neuropsychiatric recovery following chronic MA dependence by reducing neuroinflammation and by addressing hyper-reactivity to neuroantigen.
Aim 1: In humans, we will identify peripheral immune factors most significantly impacted by chronic MA dependence and which correspond with MA-induced neuropsychiatric impairments.
Aim 2: In humans, we will fully characterize the effects of chronic MA dependence on peripheral immune cell function as measured by in vitro reactivity to neuroantigens and other antigens, and to characterize the relationship between MA induced neuropsychiatric impairment and altered peripheral immunoreactivity.
Aim 3: In mice, we will evaluate the therapeutic activity of one novel immunotherapy in reducing MA-induced neuropsychiatric impairments, central nervous system (CNS) injury, neuroinflammation, and trafficking of neuroantigen-reactive immune cells from the periphery to the CNS.