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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Authors of this month's paper.
Authors of this month's paper.
Featured paper of the Month!

JANUARY: SERCaMP: a carboxy-terminal protein modification that enables monitoring of ER calcium homeostasis

Mol Biol Cell. 2014 Sep 15;25(18):2828-39

Mark J. Henderson, Emily S. Wires, Kathleen A. Trychta, Christopher T. Richie, and Brandon K. Harvey

Abstract: Endoplasmic reticulum (ER) calcium homeostasis is disrupted in diverse pathologies, including neurodegeneration, cardiovascular diseases, and diabetes. Temporally defining calcium dysregulation during disease progression, however, has been challenging. Here we describe secreted ER calcium-monitoring proteins (SERCaMPs), which allow for longitudinal monitoring of ER calcium homeostasis....

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A figure from this month's Review A figure from this month's Review
Reviews to Read

DECEMBER: Curious cases: Altered dose–response relationships in addiction genetics

George R. Uhl, Jana Drgonova, F. Scott Hall

Dose-response relationships for most addictive substances are "inverted U"-shaped. Addictive substances produce both positive features that include reward, euphoria, anxiolysis, withdrawal-relief, and negative features that include aversion, dysphoria, anxiety and withdrawal symptoms. A simple model differentially associates ascending and descending limbs of dose-response curves with rewarding and aversive influences, respectively. However, Diagnostic and Statistical Manual (DSM) diagnoses of substance dependence fail to incorporate dose-response criteria and don't directly consider balances between euphoric and dysphoric drug effects. Classical genetic studies document substantial heritable influences on DSM substance dependence....

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!

DECEMBER: Intravenous ghrelin administration increases alcohol craving in alcohol-dependent heavy drinkers: a preliminary investigation.

Biol Psychiatry. 2014 Nov 1;76(9):734-41

Lorenzo Leggio, William H. Zywiak, Samuel R. Fricchione, Steven M. Edwards, Suzanne M. de la Monte, Robert M. Swift, and George A. Kenna

Background: There is a need to identify novel pharmacologic targets to treat alcoholism. Animal and human studies suggest a role for ghrelin in the neurobiology of alcohol dependence and craving. Here, we were the first to test the hypothesis that intravenous administration of exogenous ghrelin acutely increases alcohol craving....

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Dr. Steven Goldberg Dr. Steven Goldberg
A note from Michael Gottesman on the death of Dr. Steven Goldberg

Steven Goldberg, chief of NIDA's Pre-Clinical Pharmacology Section, died on November 25 of a sudden cardiac arrest at age 73.

This is tragic news for his family -- his wife and children, one of whom is still in high school -- as well as for NIDA and the addiction field, given Steve's outstanding contributions to our understanding of the behavioral and neuropharmacological mechanisms triggered by drugs of abuse.

NIDA Director Nora Volkow, in her message to NIDA staff yesterday, wrote how "we are left with the nagging feeling that the best was yet to come."

Steve's family will hold a private funeral in the Boston area shortly after Thanksgiving and hopes to host a service locally in the near future.

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Drug and Alcohol Dependence Drug and Alcohol Dependence.
Reviews to Read

NOVEMBER: Synthetic cannabinoids: Epidemiology, pharmacodynamics, andclinical implications

Marisol S. Castaneto, David A. Gorelick, Nathalie A. Desrosiers, Rebecca L. Hartman, Sandrine Pirard, Marilyn A. Huestis

Synthetic cannabinoids (SC) are a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently utilized published data to develop SC variations marketed as abusable designer drugs. In the early 2000s, SC became popular as "legal highs" under brand names such as Spice and K2, in part due to their ability to escape detection by standard cannabinoid screening tests. The majority of SC detected in herbal products have greater binding affinity to the cannabinoid CB1 receptor than does Δ9-tetrahydrocannabinol (THC), the primary psychoactive compound in the cannabis plant, and greater affinity at the CB1 than the CB2 receptor....

Read the full review at PubMed.

The graphical abstract for this paper. The graphical abstract for this paper.
Hot off the Press!

Serotonergic versus Nonserotonergic Dorsal Raphe Projection Neurons: Differential Participation in Reward Circuitry

Cell Reports Volume 8, Issue 6, p1857–1869, 25 September 20143

Ross A. McDevitt, Alix Tiran-Cappello, Hui Shen, Israela Balderas, Jonathan P. Britt, Rosa A.M. Marino, Stephanie L. Chung, Christopher T. Richie, Brandon K. Harvey, and Antonello Bonci

The dorsal raphe nucleus (DRN) contains the largest group of serotonin-producing neurons in the brain and projects to regions controlling reward. Although pharmacological studies suggest that serotonin inhibits reward seeking, electrical stimulation of the DRN strongly reinforces instrumental behavior. Here, we provide a targeted assessment of the behavioral, anatomical, and electrophysiological contributions of serotonergic and nonserotonergic DRN neurons to reward processes....

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