Featured Paper of the Month

Featured Paper of the Month – January 2023
Published in Science Advances by Yi He and Zheng-Xiong Xi, et al. of the NIDA IRP Addiction Biology Unit.

It is well known that physical exercise is rewarding and protective against drug abuse and addiction. However, the neural mechanisms underlying these actions are not fully understood. In this report, we found that prolonged daily voluntary wheel-running produced a more robust increase in c-fos expression in the red nucleus (RN) than in other brain regions. Subsequent neuronal tracing imaging and electrophysiological assays demonstrated that most RN neurons are glutamatergic in its magnocellular portion (RNm) and wheel-running activates a subset of RNm glutamate neurons that project to the neighboring ventral tegmental area (VTA), particularly to contralateral VTA dopamine neurons…

Featured Paper of the Month – December 2022
Published in The Journal of Neuroscience by Clara Wolfe and Carl Lupica et al. of the NIDA IRP Electrophysiology Research Section.

The lateral habenula (LHb) is a brain region receiving information from brain areas involved in decision making, with influence on motivation, reward, and movement. This interface between thoughts, emotions, and actions is how the LHb permits adaptive behavior, and LHb dysfunction is implicated in psychiatric and drug use disorders. Silencing the LHb impairs control over cocaine seeking in rats and muscarinic acetylcholine receptors (mAChR) are also implicated…

Featured Paper of the Month – November 2022
Published in Neuropsychopharmacology by Thomas Ross and Elliot Stein of the NIDA IRP Neuroimaging Research Branch.

The striatum, part of the forebrain, is critically involved in reward processes and substance use. Many of the inputs to the striatum come from frontal brain regions. One way to study these connections in living humans is using a technique called functional magnetic resonance imaging (fMRI). A common fMRI approach, resting-state functional connectivity, typically examines the temporal similarity of the signals from two brain areas: essentially looking at the connection between ‘point A’ and ‘point B’…

Featured Paper of the Month – October 2022
Published in Proceedings of the Eighth Workshop on Computational Linguistics and Clinical Psychology by Salvatore Giorgi and Brenda Curtis, et al. of the NIDA IRP Technology and Translational Research Unit.

Nonsuicidal self-injury (NSSI), or the deliberate injuring of one’s body without intending to die, has been shown to exhibit many similarities to substance use disorders (SUDs), for example comorbidity with anxiety and depression. Research has further shown that people who self-injure adopt language common in SUD recovery or 12-step communities. Using over 150,000 comments from approximately 5,000 people posting on the social media website Reddit, we investigate the shared language of NSSI and SUD by comparing discussions on public forums related to self-injury and drug addiction…

Featured Paper of the Month – September 2022
Published in Molecular Psychiatry by Jordi Bonaventura and Michael Michaelides, et al. of the NIDA IRP Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit.

The use of racemic ketamine and the FDA approval of (S)-ketamine are promising developments for the treatment of depression. Nevertheless, racemic ketamine and (S)-ketamine are controlled substances with known abuse potential and their use is associated with undesirable side effects. For these reasons, research efforts have focused on identifying alternatives. One candidate is (2R,6R)-hydroxynorketamine ((2R,6R)-HNK), a ketamine metabolite that in animal studies lacks the dissociative and abuse properties of ketamine while retaining its antidepressant-like behavioral efficacy…

Featured Paper of the Month – August 2022
Published in The Journal of Neuroscience by Hong-Ju Yang, Briana J Hempel, and Zheng-Xiong Xi, et al. of the NIDA IRP Addiction Biology Unit.

It is well known that glutamate plays an important role in relapse to drug seeking. However, the role of glutamate in drug reward is unclear. In this report, we found that elevating extracellular glutamate level in the nucleus accumbens (NAc) by TFB-TBOA, a selective astrocyte glutamate transporter inhibitor, dose-dependently inhibits cocaine self-administration and brain-stimulation reward. Mechanistic assays indicate that prolonged cocaine self-administration selectively upregulates NMDA-GluN2B receptor subtype expression in striatal dopaminoceptive neurons…

Featured Paper of the Month – July 2022
Published in Frontiers in Pharmacology by Kirsten Smith, Ph.D.; Jeffrey Rogers, BS., B.A.; and David Epstein, Ph.D.; et al. of the NIDA IRP Real-world Assessment, Prediction, and Treatment Unit.

Kratom is a plant increasingly used in the US for the psychoactive properties of the more than four dozen alkaloids it contains. Their mechanisms of action are thought to be opioidergic, adenosinergic, serotoninergic, dopaminergic, and adrenergic. Whole-plant-derived kratom products, almost always taken orally, produce dose-dependent stimulatory and analgesic effects. We know of only one published laboratory study on kratom’s effects in humans; however, surveys have increasingly helped show a complex and changing landscape of kratom use. In this online, nationwide study, we asked 129 people with kratom use histories to report on the effects of their kratom products…

Featured Paper of the Month – June 2022
Published in Neuropsychopharmacology by Zhi-Bing You, Ph.D. and Eliot Gardner, Ph.D., et al. of the NIDA IRP Neuropsychopharmacology Section.

Cocaine addiction is a significant medical and public concern.  Despite decades of research effort, development of anti-addiction, anti-craving, and anti-relapse medications for cocaine addiction remains largely unsuccessful.  To aid this medication development, more knowledge is needed about the brain circuits and mechanisms that underlie addiction.  In the present article, the authors show that: (1) elevation of the brain hormone ghrelin by cocaine plays a critical role in cocaine-taking and in cocaine-seeking behaviors;  (2) acquisition of cocaine-taking behavior is associated with enhancement of the stimulatory effects of cocaine and of cocaine-associated environmental cues on brain ghrelin…

Featured Paper of the Month – May 2022
Published in Neuropsychopharmacology by Grant Glatfelter, John Partilla and Michael Baumann of the NIDA IRP Designer Drug Research Unit.

5F-MDMB-PICA is a potent synthetic cannabinoid associated with public harm from recreational use. Little is known about the pharmacology of 5F-MDMB-PICA underlying it’s potent effects. This study examined the pharmacological effects of 5F-MDMB-PICA at cannabinoid type 1 receptors (CB1) in mice relative to several structurally related compounds. Results show that certain structural features of the “head” groups of 5F-MDMB-PICA and related compounds dramatically impacts their potencies for CB1 mediated pharmacological effects and for producing cannabinoid-like effects in mice, which is predictive of potency of these compounds in humans…

Featured Paper of the Month – April 2022
Published in Cell Reports by Justin Siemian and Yeka Aponte, et al. of the NIDA IRP Neuronal Circuits and Behavior Unit.

The lateral hypothalamus (LH) has long been known for its involvement in feeding behaviors. Specifically, GABAergic LH (LH^VGAT) neurons are known to mediate food intake (consummatory) and food-seeking (appetitive) behaviors, but GABAergic neurons comprise a large population of neurons that can further be divided into genetically identified subpopulations. Therefore, we sought to determine the function of a subset of LH^VGAT neurons identified as leptin receptor-expressing neurons (LH^LEPR neurons). We used a combination of neuronal ablation, optogenetics, chemogenetics, and in vivo calcium imaging to study the contributions of LH^LEPR neurons to the greater LH^VGAT population in mice…