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Our People
The IRP is served by the best and brightest in the scientific community. Find out more about the scientists striving to solve the puzzles of drug addiction and its effects on the human brain.
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Our Research
The research of the Intramural Research Program is supported at the molecular, genetic, cellular, animal, and clinical levels and is conceptually integrated, highly innovative, and focused on major problems in the field of drug addiction research.
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Our Organization
Intramural Research Program (IRP) of the National Institute on Drug Abuse is dedicated to innovative research on basic mechanisms that underlie drug abuse and dependence, and to develop new methods for the treatment of drug abuse and dependence.
Dr. Stephen Heishman
Associate Director for Education & Training
and Summer Student training
opportunities available!
Dr. Jean Lud Cadet
Associate Director for Diversity and Outreach
Fellowship for Diversity
in Research available!
Dr. Yuji Takahashi and Dr. Geoffrey Shoenbaum.
MAY: Expectancy-related changes in firing of dopamine neurons depend on orbitofrontal cortex
Nature Neuroscience 14, 1590–1597 (2011) doi:10.1038/nn.2957
Received 14 July 2011 | Accepted 15 September 2011 | Published online 30 October 2011
Yuji K Takahashi, Matthew R Roesch, Robert C Wilson, Kathy Toreson, Patricio O’Donnell, Yael Niv & Geoffrey Schoenbaum
The orbitofrontal cortex has been hypothesized to carry information regarding the value of expected rewards. Such information is essential for associative learning, which relies on comparisons between expected and obtained reward for generating instructive error signals. These error signals are thought to be conveyed by dopamine neurons. To test whether orbitofrontal cortex contributes to these error signals, we recorded from dopamine neurons in orbitofrontal-lesioned rats performing a reward learning task. Lesions caused marked changes in dopaminergic error signaling....
Matthew T. Sutherland, Meredith J. McHugh, Vani Pariyadath
Resting state functional connectivity in addiction: Lessons learned and a road ahead
Despite intensive scientific investigation and public health imperatives, drug addiction treatment outcomes have not significantly improved in more than 50 years. Non-invasive brain imaging has, over the past several decades, contributed important new insights into the neuroplastic adaptations that result from chronic drug intake, but additional experimental approaches and neurobiological hypotheses are needed to better capture the totality of the motivational, affective, cognitive, genetic and pharmacological complexities of the disease. Recent advances in assessing network dynamics through resting-state functional connectivity (rsFC) may allow for such systems-level assessments. In this review, we first summarize the nascent addiction-related rsFC literature and suggest that in using this tool, circuit connectivity may inform specific neurobiological substrates underlying psychological dysfunctions associated with reward, affective and cognitive processing often observed in drug addicts....
Dr. Federica Lucantonio, Review Author
The impact of orbitofrontal dysfunction on cocaine addiction
Cocaine addiction is characterized by poor judgment and maladaptive decision-making. Here we review evidence implicating the orbitofrontal cortex in such behavior. This evidence suggests that cocaine-induced changes in orbitofrontal cortex disrupt the representation of states and transition functions that form the basis of flexible and adaptive model-based behavioral control. By impairing this function, cocaine exposure leads to an overemphasis on less flexible, maladaptive model-free control systems. We propose that such an effect accounts for the complex pattern of maladaptive behaviors associated with cocaine addiction.
Article published online, October 30, 2011 in Nature Neuroscience.
Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors
Nature Neuroscience advance online publication 30 October 2011; doi: 10.1038/nn.2940
Elena E Bagley, Jennifer Hacker, Vladimir I Chefer, Christophe Mallet, Gavan P McNally, Billy C H Chieng, Julie Perroud, Toni S Shippenberg, MacDonald J Christie
Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations....
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