Featured Paper of the Month

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…

Featured Paper of the Month – November 2021
Published in Brain Communications by Tianye Zhai and Yihong Yang et al. in the NIDA IRP Magnetic Resonance Imaging and Spectroscopy Section.

Cocaine use disorder is a highly relapsing chronic brain disease with current treatments relatively ineffective. Finding brain areas and brain functional circuits that are relevant to cocaine relapse is crucial in understanding the brain mechanisms of addiction as well as in developing effective treatment protocols. By combining the resting-state fMRI and the Cox regression based predictive modeling, Zhai et al. identified three sets of dorsolateral prefrontal cortex (dlPFC)-centric functional circuits that predict cocaine relapse with high accuracy, provide insights into the multiple roles ofthe dlPFC in brain functioning that affect treatment outcome, and suggest these dlPFC loci as potential neuromodulation targets for addiction treatment…

Featured Paper of the Month – October 2021
Published in Neuropharmacology by Agustin Zapata and Carl R Lupica  in the NIDA IRP Electrophysiology Research Section.

Studies show that cannabis increases relapse to cocaine seeking following withdrawal, and in humans cannabis and cocaine use are associated with impulse control deficits. We showed previously that an area of the brain known as the lateral habenula (LHb) is involved in inhibiting operant responses for cocaine in rat self-administration studies. Therefore, the present study was conducted to determine if the LHb controls impulsivity caused by acute cocaine or the primary psychoactive component of cannabis know as Δ9-tetrahydrocannabinol (Δ9-THC)…

Featured Paper of the Month – September 2021
Published in Addiction Biology by  Sara Deschaine, Mehdi Farokhnia, and Lorenzo Leggio et al. in the NIDA IRP Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section.

Growing evidence shows that ghrelin, a gastric-derived peptide hormone, is involved in regulation of alcohol seeking behavior. Accordingly, the ghrelin system is being studies as a potential pharmacotherapeutic target for alcohol use disorder (AUD). The reverse side of this bidirectional link, i.e., the effects that alcohol may have on the ghrelin system, is not well understood. In a series of preclinical and clinical experiments, the present study aimed to investigate the impact of alcohol on different elements of the ghrelin system.

Featured Paper of the Month – August 2021
Published in European Journal of Neuroscience by  Jorge Miranda-Barrientos and Marisela Morales, et al. in the NIDA IRP Neuronal Networks Section.

The ventral tegmental area (VTA) contains dopamine neurons intermixed with GABA-releasing (expressing vesicular GABA transporter, VGaT), glutamate-releasing (expressing vesicular glutamate transporter 2, VGluT2), and glutamate-GABA co-releasing (co-expressing VGluT2 and VGaT) neurons. By delivering INTRSECT viral vectors into the VTA of double vglut2-Cre/vgat-Flp transgenic mice, we targeted specific VTA cell populations for ex vivo recordings. We found that VGluT2+ VGaT- and VGluT2+ VGaT+ neurons on average had relatively hyperpolarized resting membrane potential, greater rheobase, and lower spontaneous firing frequency compared to VGluT2- VGaT+ neurons, suggesting that VTA glutamate-releasing and glutamate-GABA co-releasing neurons require stronger excitatory drive to fire than GABA-releasing neurons…