Featured Paper of the Month

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…

Featured Paper of the Month – March 2022
Published in Cerebral Cortex by Thomas Ross and Elliot Stein of the NIDA IRP Cognitive and Affective Neuroscience of Addiction Section.

The right and left hemispheres of the brain each play a dominant role in certain functions, such as inhibitory control (right) and language (left). Differences in the structure and connections of the right and left hemispheres (i.e., “lateralities”) help to facilitate these functional specialties. Yet, in several neurodevelopment and neuropsychiatric disorders – including addiction – these hemispheric lateralities appear to be abnormal. In this paper, NIDA scientists provide a normative description of laterality in the circuits that connect the frontal cortex to the striatum – a system centrally implicated in addiction…

Featured Paper of the Month – February 2022
Published in Translational Psychiatry by Daria Piacentino and Lorenzo Leggio, et al. of the NIDA IRP Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section.

Chronic excessive alcohol drinking causes more than 80,000 deaths in the U.S. each year. The gut microbiota, which hosts more than a trillion bacteria, is gaining increasing attention as a potential modulator in neuropsychiatric disorders. Its diversity is fundamental in maintaining homeostasis. There is limited research on the role of the microbiome-gut-brain axis in alcohol use disorder. Dr. Daria Piacentino and her colleagues address the fundamental question on whether chronic excessive alcohol drinking affects the gut microbiome and metabolome in a baboon model, investigated under rigorous controlled experimental conditions…

Featured Paper of the Month – January 2022
Published in Translational Psychiatry by Juan Gomez and Michael Michaelides of the NIDA IRP Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit.

Cocaine binds to the dopamine (DA) transporter (DAT) to regulate cocaine reward and seeking behavior. Zinc also binds to the DAT, but the in vivo relevance of this interaction is unknown. We examined this interaction by altering zinc availability and measuring behavior and physiology associated with cocaine exposure. To alter zinc levels, we manipulated dietary zinc or used a mouse model that lacked the zinc transporter ZnT3. The body has no storage system for zinc and one must consistently replenish this essential element via zinc-rich food sources. Of the 24 transporters dedicated to moving zinc around the body, ZnT3 is necessary to shuttle zinc around the brain…

Featured Paper of the Month – December 2021
Published in Current Biology by Justin Siemian, Sarah Sarsfield, Yeka Aponte of the NIDA IRP Neuronal Circuits and Behavior Unit.

Regulating food intake is essential for survival and many factors influence feeding behaviors beyond caloric need or “hunger”. Despite this, some neurons that drive feeding in mice are routinely referred to as ‘‘hunger neurons,’ whereas others are not. To understand how specific hypothalamic neurons control interoceptive hunger, we trained mice to discriminate feelings of “hunger” from satiety. We then used optogenetics to manipulate the activity of three hypothalamic neuronal populations with well-known effects on feeding while mice performed this behavioral task…