Molecular Neurobiology Research Branch
Molecular Neurobiology Section
Mission Statement
The Molecular Neurobiology Branch works to improve understanding of drug abuse causes and mechanisms. We seek insights likely to improve therapeutics and enhance matching of drug abuse prevention and treatments to individual strengths and vulnerabilites. Insights from these studies inform work in related areas, including aging, movement and sleep disorders, personality and pain. We define alleles and locus-specific phenotypes that contribute to the genetic bases of abused substance vulnerabilities in humans and mouse models. We find genes whose products and/or regulation are important for the acute and long-term actions of abused substances, and continue efforts to define molecular underpinnings of drug reward, reinforcement and addiction. These challenging tasks require closely interactive work from the Molecular Neurobiology and Molecular Genetics sections of the Branch.
Program Areas
• To continually improve understanding of abused substance receptors so that knowledge about molecular and cellular bases of drug actions can be refined and therapeutic strategies improved.
• Defining the detailed distribution of mu receptors:
• Dopaminergic and Monoaminergic Transporters and Genes
• Identifying drug-regulated genes
• To model and seek genetic bases for individual differences in drug responses and drug abuse vulnerabilities
• The Branch is committed to training staff members, and is pleased with the roles that former fellows are playing in academic, government and industrial settings. The Branch structure has allowed outstanding individuals to progress and develop managerial as well scientific expertise at the intersection of pharmacology, molecular neurobiology and genetics.
Name: George R. Uhl, M.D., Ph.D.
Title: Chief, Molecular Neurobiology Branch
Telephone Number: (410) 550-1538
Synopsis of Research
• Identify allelic variants that predispose to human substance abuse vulnerability and animal models of this vulnerability, to elucidate phenotypes that individual loci confer singly and interactively, and to develop such information to improve treatment and prevention strategies
• Develop and use genome scanning methods to identify chromosomal loci that harbor alleles that contribute to human substance abuse vulnerability: a “top down” strategy
• To use neurobiologic, genomic, mouse model and other strategies to identify influences of allelic variants in candidate genes in humans and mice: a “bottom up” strategy
• Identify genes and proteins regulated acutely and chronically by addictive substances and by alterations in the expression of drug “receptors”
• To enhance understanding of the ways in which the single or multiple molecular targets of psychostimulants and other drugs contribute to drug reward, aversive consequences of drug administration and to the adaptive and learned alterations that drugs confer to yield tolerance, dependence and other addictive phenomena
• To follow interesting leads concerning candidate gene involvement in other physiological and pathological processes, including pain, sleep, aging and Parkinsonian neurodegenerations.
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Molecular Neurobiology Research Branch
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