The Intramural Research Program of the National Institute on Drug Abuse

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    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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    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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    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.

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Jordi Bonaventura.
Jordi Bonaventura.
Hot off the Press!

Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer

PNAS June 22, 2015, doi: 10.1073/pnas.1507704112

Jordi Bonaventura, Gemma Navarro, Verònica Casadó-Anguera, Karima Azdad, William Rea, Estefanía Moreno, Marc Brugarolas, Josefa Mallol, Enric I. Canela, Carme Lluís, Antoni Cortés, Nora D. Volkow, Serge N. Schiffmann, Sergi Ferré, and Vicent Casadó

Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R....

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A figure from this paper. A figure from this paper.
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Role of corticostriatal circuits in context-induced reinstatement of drug seeking

Nathan J.Marchant, Konstantin Kaganovsky, Yavin Shaham, Jennifer M. Bossert

Drug addiction is characterized by persistent relapse vulnerability during abstinence. In abstinent drug users, relapse is often precipitated by re-exposure to environmental contexts that were previously associated with drug use. This clinical scenario is modeled in preclinical studies using the context-induced reinstatement procedure, which is based on the ABA renewal procedure. In these studies, context-induced reinstatement of drug seeking is reliably observed in laboratory animals that were trained to self-administer drugs abused by humans....

Read the full review at PubMed.

A figure from this month's paper.
A figure from this month's paper.
Featured paper of the Month!

JUNE: R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

Neuropsychopharmacology 2015 Jun;40(7):1762-71

Xiao-Fei Wang, Guo-Hua Bi, Yi He, Hong-Ju Yang, Jun-Tao Gao, Oluyomi M Okunola-Bakare, Rachel D Slack, Eliot L Gardner, Zheng-Xiong Xi, and Amy Hauck Newman

(±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions....

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A figure from this paper. Dr. Jean Lud Cadet.
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Epigenetics of Stress, Addiction, and Resilience: Therapeutic Implications

Jean Lud Cadet

Abstract Substance use disorders (SUDs) are highly prevalent. SUDs involve vicious cycles of binges followed by occasional periods of abstinence with recurrent relapses despite treatment and adverse medical and psychosocial consequences. There is convincing evidence that early and adult stressful life events are risks factors for the development of addiction and serve as cues that trigger relapses. Nevertheless, the fact that not all individuals who face traumatic events develop addiction to licit or illicit drugs suggests the existence of individual and/or familial resilient factors that protect these mentally healthy individuals....

Read the full review at PubMed.

A figure from this month's paper.
A figure from this month's paper.
Featured paper of the Month!

MAY: Central role for the insular cortex in mediating conditioned responses to anticipatory cues

PNAS January 27, 2015 vol. 112 no. 4 1190-1195

Ikue Kusumoto-Yoshida, Haixin Liu, Billy T. Chen, Alfredo Fontanini, and Antonello Bonci

Reward-related circuits are fundamental for initiating feeding on the basis of food-predicting cues, whereas gustatory circuits are believed to be involved in the evaluation of food during consumption. However, accumulating evidence challenges such a rigid separation. The insular cortex (IC), an area largely studied in rodents for its role in taste processing, is involved in representing anticipatory cues. Although IC responses to anticipatory cues are well established, the role of IC cue-related activity in mediating feeding behaviors is poorly understood....

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A figure from this month's paper.
A figure from this month's paper.
Hot off the Press!

Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35 turnover via myristic acid

PNAS May 11, 2015, doi: 10.1073/pnas.1422001112

Shang-Yi A. Tsai, Michael J. Pokrass, Neal R. Klauer, Hiroshi Nohara, and Tsung-Ping Su

Dysregulation of cyclin-dependent kinase 5 (cdk5) per relative concentrations of its activators p35 and p25 is implicated in neurodegenerative diseases. P35 has a short t½ and undergoes rapid proteasomal degradation in its membrane-bound myristoylated form. P35 is converted by calpain to p25, which, along with an extended t½, promotes aberrant activation of cdk5 and causes abnormal hyperphosphorylation of tau, thus leading to the formation of neurofibrillary tangles....

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The National Institute on Drug Abuse (NIDA), is part of the National Institutes of Health (NIH), the principal biomedical and behavioral research agency of the United States Government. NIH is a component of the U.S. Department of Health and Human Services.

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