The career development and mentorship plan described in this application will allow the applicant to continue the development and expansion of his research career into new areas of investigation that complement current areas of expertise. Specifically, I will have the opportunity to acquire new skills and expertise with MRI i functional connectivity and vascular pathology. I will collaborate with Dr. Mark Goodman on the development of novel biomarkers for PET in order to expand neuropharmacological targets beyond monoamine transporters. I also will initiate self-administration and PET neuroimaging studies at the Yerkes Field Station in order to focus on ethologically-relevant models of social behavior and drug use through collaboration with Dr. Mark Wilson. I plan to commit 75% effort during the five-year period of support in order to continue to advance my career in substance abuse research and enhance my role as a mentor. Approximately 50% effort will be devoted to the conduct of experiments once all research protocols are standardized. The proposed prospective studies in nonhuman primates will document the relevant neurochemical and functional changes that occur during cocaine use and apply this knowledge to evaluate the effectiveness of extinction therapy augmented with pharmacological intervention in normalizing brain function and preventing reinstatement as an animal model of drug relapse. These data will provide insights on pharmacological targets for future medications development, thus accelerating the discovery of effective treatments. Related studies will provide information concerning the basic role of serotonin in the regulation of dopaminergic function as it relates to the neuropharmacology of cocaine. These translational studies in nonhuman primates will determine the effectiveness of the serotonin system to modulate the abuse-related behavioral and neurochemical effects cocaine. Collectively, the integration of behavioral pharmacology, in vivo neurochemistry and functional neuroimaging will enhance our understanding of the neurobiological mechanisms involved in cocaine self- administration and reinstatement in nonhuman primates. Another 25% effort will be committed to mentoring of new, independent investigators. I plan to serve as the primary mentor of two junior faculty and as a secondary mentor for two additional faculty at the rank of Instructor or Assistant Professor. Through mentoring young scientists with broad areas of expertise, I will expand the breadth of techniques and general approaches applied to drug addiction research. The remaining 25% effort not supported by the Senior Scientist Research and Mentorship Award will be committed to University administrative responsibilities, other research-related pursuits consistent with the objectives of the award, including oversight of graduate students and postdoctoral fellows, and educational activities. The long-term commitment and support provided by a Senior Scientist Research and Mentorship Award will allow the implementation of these integrated techniques to novel research applications, and provide effective mentorship for new, independent investigators with an interest in drug addiction.
The objective of the present proposal is to identify potential therapeutic targets for the treatment of stimulant abuse and dependence. These translational studies in nonhuman primates will determine the effectiveness of the serotonin system to modulate the behavioral and neurochemical effects cocaine, and document relevant changes in neurochemistry, brain metabolism and functional activity that occur during the progression of drug dependence and addiction. Moreover, significant effort will be committed to the mentorship of new, independent investigators focused on drug addiction research.
|Curry, Daniel W; Young, Matthew B; Tran, Andrew N et al. (2018) Separating the agony from ecstasy: R(-)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice. Neuropharmacology 128:196-206|
|Young, Matthew B; Howell, Leonard L; Hopkins, Lauren et al. (2018) A peripheral immune response to remembering trauma contributes to the maintenance of fear memory in mice. Psychoneuroendocrinology 94:143-151|
|Pitts, Elizabeth G; Curry, Daniel W; Hampshire, Karly N et al. (2018) (±)-MDMA and its enantiomers: potential therapeutic advantages of R(-)-MDMA. Psychopharmacology (Berl) 235:377-392|
|Berro, Laís F; Shields, Hannah; Odabas-Geldiay, Melis et al. (2018) Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) and R(-) MDMA on actigraphy-based daytime activity and sleep parameters in rhesus monkeys. Exp Clin Psychopharmacol 26:410-420|
|Pitts, Elizabeth G; Minerva, Adelaide R; Chandler, Erika B et al. (2017) 3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel Monkeys in a Serotonin 2A Receptor-Dependent Manner. Neuropsychopharmacology 42:1962-1971|
|Berro, Laís F; Andersen, Monica L; Howell, Leonard L (2017) Assessment of tolerance to the effects of methamphetamine on daytime and nighttime activity evaluated with actigraphy in rhesus monkeys. Psychopharmacology (Berl) 234:2277-2287|
|Maltbie, Eric A; Kaundinya, Gopinath S; Howell, Leonard L (2017) Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action. Behav Pharmacol 28:610-622|
|Berro, Laís F; Perez Diaz, Maylen; Maltbie, Eric et al. (2017) Effects of the serotonin 2C receptor agonist WAY163909 on the abuse-related effects and mesolimbic dopamine neurochemistry induced by abused stimulants in rhesus monkeys. Psychopharmacology (Berl) 234:2607-2617|
|Young, Matthew B; Norrholm, Seth D; Khoury, Lara M et al. (2017) Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA). Psychopharmacology (Berl) 234:2883-2895|
|Berro, Laís F; Andersen, Monica L; Tufik, Sergio et al. (2017) GABAA receptor positive allosteric modulators modify the abuse-related behavioral and neurochemical effects of methamphetamine in rhesus monkeys. Neuropharmacology 123:299-309|
Showing the most recent 10 out of 35 publications