David V. Herin - US grants

DESCRIPTION: (Provided by Applicant): Abuse of the substituted amphetamine 3,4-Methylenedioxymethamphetamine (MDMA) has rapidly increased in recent years, particularly among adolescents. Users report that MDMA elevates mood and confidence and increases connectedness with others. However, MDMA has also been shown to produce undesirable alterations in mood, sleep, memory, and thermoregulation. The exact mechanisms of action for MDMA are unknown, but are thought to be mediated partly through MDMA-induced serotonin release via reversal of the serotonin transporter. Since serotonin release is important in mediating the effects of MDMA, our lab has focused on determining the role of specific serotonin receptors in the behavioral effects of MDMA. Preliminary data suggest that activation of the 5-HT2A receptor is important in generating hyperlocomotor activity elicited by MDMA, and the literature suggests that serotonin plays a role in the generation of MDMA-induced conditioned place preference (CPP). Both CPP and locomotor activity are generated by activation of the mesoaccumbens dopamine pathway. Therefore, the purpose of this proposal is to determine the involvement of 5-HT2A receptors in the hyperlocomotive and conditioned stimulus effects of MDMA.

[unreadable] DESCRIPTION (provided by applicant): This application requests support for a NIDA Pathway to Independence award (K99 ROO) enabling David Herin, Ph.D, to develop the skills necessary for an independent research career investigating pharmacological treatments for substance abuse. Dr. Herin possesses a unique combination of experience and expertise that will be a tremendous asset as he develops into an independent researcher. The applicant's predoctoral training with Dr. Kathryn Cunningham established clear expertise in preclinical neuropharmacology. Notably, he investigated the ability of pharmacotherapeutic agents to block the behavioral and physiological effects of psychostimulants in rodents. His interest in translational research led him to pursue a postdoctoral fellowship in the NIDA-funded medication development unit (P50) led by Dr. John Grabowski, where a well formulated post-doctoral plan provided training for Dr. Herin in many facets of clinical research. The mentored portion of the proposed multidisciplinary research plan provides Dr. Herin with the opportunity to gain additional expertise in development, implementation, and analysis of substance use disorder clinical trials, including a pilot study examining the ability of dextroamphetamine to treat individuals with comorbid cocaine dependence and attention-deficit hyperactivity disorder (ADHD). In addition, Dr. Herin will obtain extensive experience in statistical analysis of these studies, and collaborate with department faculty in ongoing functional imaging studies. Training will be provided via didactic instruction and individualized guidance from faculty members with expertise in clinical trial design, statistical analysis, and functional imaging. This multidisciplinary training will culminate in implementation of a large scale clinical trial assessing the efficacy of dextroamphetamine to treat comorbid ADHD and cocaine dependence. In all, the proposed training will provide a unique, exceptional expertise that will permit Dr. Herin to make significant scientific contributions and embark on a successful career in translational drug abuse research. [unreadable] [unreadable] [unreadable] [unreadable]

This proposal requests support for the ROO phase of the K99/R00 Pathway to Independence Award enabling David Herin, Ph.D, to begin his independent career investigating pharmacological treatments for substance abuse. The first (K99) phase ofthis award has been conducted at the University of Texas Health Science Center at Houston (UTHSC) under Drs. John Grabowski and Joy Schmitz. In this phase, Dr. Herin completed training in clinicai trials metholodology, advanced statistical methods, the responsible conduct of research, as well as u-aining in professional skills. Additionally, Dr. Herin obtained experience in implementation of clinical trials in multiple studies at the UTHSC P50 medication development center, and developed collaborations with departmental faculty. This clinical training has enabled Dr. Herin lo secure a tenure-track faculty position in the Department of Psychiatry at the University of Minnesota. As Dr. Herin launches his independent career, ROO support will enable him to conduct a clinical trial investigating the ability of lisdexamfetamine to treat cocaine dependence. During this ROO period, Dr. Herin will also develop collaborations with his University of Minnesota colleagues in fields such as functional imaging, impulsivity, genetics, and human laboratory studies, enabling submission of future interdisciplinary grant applications to funding agencies. In all, the K99 and ROO awards permit Dr. Herin to begin his independent career and make significant scientific contributions to the field of substance abuse research.