Molecular Neurobiology of Drug Addiction
To improve our understanding of the biological basis of addiction
a NIDA Program Project Grant

About the Program

Addiction remains one of the world’s greatest public health problems, yet its pathophysiology remains incompletely understood and available treatments for addictions to various drugs of abuse are inadequately effective for most people. We believe that the most effective way of eventually developing definitive treatments and cures for addiction rests in part in a better understanding of its underlying neurobiology. Read more about drug addiction.

The objective of this Program Project Grant (PPG) is to fundamentally advance our understanding of the molecular and cellular mechanisms that underlie stimulant and opiate addiction. We focus on the brain's reward regions, in particular, the midbrain ventral tegmental area (VTA) and several of its forebrain projection regions, including the nucleus accumbens (NAc) and prefrontal cortex (PFC). We utilize a wide range of cutting-edge technologies to explicate the molecular, cellular, and circuit basis of addiction, including a focus on chromatin biology, so-called epigenetics, as well as advanced neurophysiological methods, state-of-the-art optogenetic tools, and sophisticated animal models of addiction. Importantly, our PPG has a strong translational component in that we validate key findings from animal models in homologous brain regions of addicted humans examined postmortem. In turn, new insight from studies of human brain feeds back and informs our animal research to explore the underlying molecular and cellular mechanisms involved. 

The PPG is composed of two Scientific Cores and four Projects:

Transgenic-Molecular Core (PI, Li Shen, Mount Sinai)
Behavioral Core (PI, Vanna Zachariou, Mount Sinai)
Project 1: Repressive Histone Methylation and Related Chromatin Changes in Opiate and Cocaine Addiction (PI, Eric Nestler, Mount Sinai)
Project 2: Cellular Studies of Drug Action (PI, Rob Malenka, Stanford University)
Project 3: Neurobiology of Drug Reward and Relapse (PI, David Self, UT Southwestern)
Project 4: Molecular Targets for Addiction in Human Reward Circuits (PI, Yasmin Hurd, Mount Sinai)


Icahn School of Medicine

Stanford University

UT Southwestern