INHIBITORY CONTROL AND METHAMPHETAMINE DEPENDENCE MODAFINIL EFFECTS

慢性甲基苯丙胺（MA）滥用与额纹状体功能标志物的缺陷有关。

Chronic methamphetamine (MA) abuse is associated with deficits in markers for frontostriatal function. Available data suggest that a variety of behavioral impairments, including diminished capacity for response inhibition, accompany this dysfunction. Impaired capacity for response inhibition may compromise treatment outcomes, and contribute to the unusually rapid progression from MA abuse to addiction. In the applicant laboratories, we have recently initiated work, using functional and structural magnetic resonance imaging, to identify the neural systems associated with response inhibition deficits in MA abusers, 2) to relate behavioral deficits to frontostriatal gray matter using novel computational brain-mapping techniques, and 3) to assess effects of modafinil (200 mg) on performance and brain function of MA-dependent and control participants during tasks that require response inhibition ("Neural Systems, Inhibitory Control, and Methamphetamine Dependence" R01DA020726, E. London, PI). This ongoing work will be integrated within the proposed Translational Center by Project 1, such that MA-dependent participants who complete cognitive tests and structural and functional MRI in Project 1 (n = 30) will proceed directly to Center Project 2 ("Inhibitory Control & MA Self-Administration: Modafinil Effects") in sufficient numbers to allow correlation analyses across projects. Project 1 will extend the R01 by administering the same protocol to 11 additional subjects, augmenting the R01 sample of 19 MA-dependent subjects currently scheduled to complete the research protocol during the Translational Center study period to a total of 30 subjects. Project 1 will thereby be able to explore research questions currently not addressed by the existing R01. New analyses carried out in Project 1 include assessing the relationship between effects of modafinil on MA self-administration (Project 2), and effects of modafinil on brain activation during inhibitory control (Project 1). We will also employ brain surface matching techniques to relate MA self-administration and MA subjective response (Project 2) to local volumes in a priori regions of interest (inferior frontal gyrus, caudate, and putamen; Project 1). By increasing the sample size of our ongoing imaging project, and integrating this work with the other Translational Center projects, the brain imaging and behavioral results of Project 1 will facilitate further productive linkages across laboratories, resulting in substantial gains in our ability to understand the neurobiology of MA-abuse and develop effective interventions.