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Branch Overview
Branch Chief: Amy Hauck Newman, Ph.D. 
The Molecular Targets and Medications Discovery Branch investigates behavioral and pharmacological mechanisms underlying the effects of drugs, such as cocaine and methamphetamine that lead to their abuse and to drug dependence. Studies of the behavioral effects of drugs, including their reinforcing and subjective effects, are designed to provide new insights into the functioning of psychoactive agents in the central nervous system (CNS), and how those actions may lead to drug abuse. Novel, small molecules are designed and synthesized as pharmacological tools to study neurochemical targets in the brain, and actions at those targets are related to the behavioral effects of abused drugs. Current targets of interest are the dopamine and serotonin transporters, dopamine (D1, D2, D3), mGluR5, and sigma receptors. The analyses of in vitro and in vivo effects of target-selective compounds provides a relation between mechanism and behavior that has led to the discovery of compounds that may prove to be leads for the development of pharmacological treatments for drug dependence and other disorders of the CNS.
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Medicinal Chemistry Section
Section Chief: Amy Hauck Newman, Ph.D.
Design, synthesis and pharmacological evaluation of:
- Atypical dopamine uptake inhibitors that bind with high affinity and selectivity to the dopamine transporter but are not cocaine-like in animal models of psychostimulant abuse
- Dopamine D3 receptor antagonists and partial agonists as in vivo tools for the elucidation of the role these receptors play in addiction and impulsive behaviors
- Allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5) as potential leads toward medications to treat drug addiction
- Fluorescent ligands to study structure and function of the dopamine and serotonin transporters
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Psychobiology Section
Section Chief: Jonathan L. Katz, Ph.D.
- Behavioral analysis of drug abuse using various procedures with animals, including intravenous drug self-administration, drug discrimination, and conditioned place preference. These procedures are used to assess mechanisms involved in the abuse of drugs.
- The relation between pharmacodynamic actions in the CNS, assessed using various techniques including in vivo microdialysis and in vivo binding and behavioral effects of abused drugs.
- Quantitative radioligand binding and in vitro functional assays to assess target affinity and selectivity of compounds designed to elucidate mechanisms underlying the behavioral effects of abused drugs.
- The application of these methods to provide new insights into the functioning of behaviorally active agents in the CNS and how these actions may lead to drug abuse, and how actions of novel compounds may be used to discover new treatments for drug dependence.
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Integrative Neurobiology Section
Section Chief: Sergi Ferré, M.D., Ph.D.
Projects include:
- Functional and pharmacological significance of neurotransmitter receptor heteromers with in vivo approaches.
- Molecular interactions involved in the quaternary structure and function of neurotransmitter receptor heteromers (cellular and molecular approaches).
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IRP Training Opportunities...
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