Stimulant addiction remains an alarming concern in society, and new therapeutic directions for prevention and treatment are required. The purpose of the present proposal is to establish the Translational Center for Serotonin and Stimulant Addiction (TCSSA) to link human, animal and cellular model systems with target and drug discovery initiatives to achieve breakthrough therapeutic advances for stimulant addiction. The initial theme emerges from clinical evidence linking addiction vulnerability traits (e.g., impulsivity, cue reactivity) to plasticity of serotonin (5-HT) neural systems. This exploratory/developmental center will (1) create a new translational research engine through complimentary, reciprocal, and synergistic interactions among clinical neurobiology, preclinical psychopharmacology, molecular/cellular biology, and drug discovery initiatives;(2) build an enhanced framework to facilitate the mentoring and career development of junior scientists in translational research;(3) conduct three integrated Projects to test the hypothesis that endophenotypic traits (impulsivity, cue reactivity) associated with cocaine dependence emerge from an imbalance in 5-HT function which will be measured at genetic (e.g., 5-HT receptor gene polymorphisms), biological (e.g., 5-HT function in platelets and brain) and systems levels (e.g., response to treatment with 5- HT medications) and that this imbalance can be normalized through selective 5-HT ligands;(4) foster the high risk/exploratory goals of designing new, targeted serotonergic molecules for neurobiology and establishing their promise as new therapeutic modalities for addiction. With the development of this new translational sphere of research activity and the generation of new protocols and paradigms, we will demonstrate that neuronal remodeling in 5-HT systems can lead to behavioral recovery in addiction and jumpstart a new generation of discovery for anti-addiction therapeutics. The future TCSSA will mature from these beginnings, and will move toward the fundamental conceptualization of bridging from molecules and chemistry, through preclinical and human laboratory research, to clinical studies, and back.

Public Health Relevance

Lay Abstract. There is a pressing need to discover effective, accessible modalities for the treatment of stimulant addiction. Through clinical and laboratory methods, we will test the ability of existing medications and the potential for newly designed drugs to enhance abstinence in stimulant-dependent individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory Grants (P20)
Project #
3P20DA024157-04S1
Application #
8467829
Study Section
Special Emphasis Panel (ZDA1-MXS-M (19))
Program Officer
Lynch, Minda
Project Start
2007-09-30
Project End
2013-12-31
Budget Start
2011-08-01
Budget End
2013-12-31
Support Year
4
Fiscal Year
2012
Total Cost
$829,243
Indirect Cost
$218,950
Name
University of Texas Medical Br Galveston
Department
Pharmacology
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Swinford-Jackson, S E; Anastasio, N C; Fox, R G et al. (2016) Incubation of cocaine cue reactivity associates with neuroadaptations in the cortical serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system. Neuroscience 324:50-61
Ma, Liangsuo; Steinberg, Joel L; Cunningham, Kathryn A et al. (2015) Inhibitory behavioral control: A stochastic dynamic causal modeling study comparing cocaine dependent subjects and controls. Neuroimage Clin 7:837-47
Anastasio, Noelle C; Stutz, Sonja J; Fink, Latham H L et al. (2015) Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity. ACS Chem Neurosci 6:1248-58
Liu, Shijing; Maili, Lorena; Lane, Scott D et al. (2015) Serotonin transporter gene promoter polymorphism predicts relationship between years of cocaine use and impulsivity. Psychiatr Genet 25:213-4
Ma, Liangsuo; Steinberg, Joel L; Cunningham, Kathryn A et al. (2015) Inhibitory behavioral control: a stochastic dynamic causal modeling study using network discovery analysis. Brain Connect 5:177-86
Fink, Latham H L; Anastasio, Noelle C; Fox, Robert G et al. (2015) Individual Differences in Impulsive Action Reflect Variation in the Cortical Serotonin 5-HT2A Receptor System. Neuropsychopharmacology 40:1957-68
Cunningham, Kathryn A; Anastasio, Noelle C (2014) Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction. Neuropharmacology 76 Pt B:460-78
Anastasio, N C; Liu, S; Maili, L et al. (2014) Variation within the serotonin (5-HT) 5-HTâ‚‚C receptor system aligns with vulnerability to cocaine cue reactivity. Transl Psychiatry 4:e369
Martin, Cédric Bp; Martin, Vincent S; Trigo, José M et al. (2014) 5-HT2C receptor desensitization moderates anxiety in 5-HTT deficient mice: from behavioral to cellular evidence. Int J Neuropsychopharmacol 18:
Fineberg, Naomi A; Chamberlain, Samuel R; Goudriaan, Anna E et al. (2014) New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity. CNS Spectr 19:69-89

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