Featured Paper of the Month

Lateral hypothalamic glutamatergic inputs to VTA glutamatergic neurons mediate prioritization of innate defensive behavior over feeding

Featured Paper of the Month – August 2024

Published in Nature Communications by Flavia Barbano and Marisela Morales, et al. of the NIDA IRP Neuronal Networks Section.

Defensive behaviors are critical actions evolutionary selected to improve survival. Barbano et al., discovered an unanticipated neuronal pathway that is activated during threatening environmental conditions.

Ecological Momentary Assessment of Self-Reported Kratom Use, Effects, and Motivations Among US Adults

Featured Paper of the Month – July 2024

Published in Jama Network Open by Kirsten Smith and David Epstein, et al. of the NIDA IRP Real-world Assessment, Prediction, and Treatment Unit.

This was the first-ever study to use real-time, app-based monitoring of patterns and consequences of kratom use, in 357 people who used kratom daily or almost daily.

Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone

Featured Paper of the Month – June 2024

Published in Molecular Psychiatry by Marjorie Levinstein and Michael Michaelides, et al. of the NIDA IRP Biobehavioral Imaging and Molecular Neuropsychopharmacology Section.

In this article we performed an in depth in vivo, in vitro, and in silico analysis of (R,S)-methadone and its enantiomers. (S)-methadone is currently in phase III trials as an antidepressant and is frequently referred to as an N-methyl-D-aspartate receptor (NMDAR) antagonist, like ketamine. Here we show that (S)-methadone, like (R)-methadone and (R,S)-methadone is an agonist at the mu opioid receptor (MOR) and does not bind to NMDARs at physiologically relevant concentrations.

Combined treatment with naloxone and the alpha2 adrenoceptor antagonist atipamezole reversed brain hypoxia induced by a fentanyl-xylazine mixture in a rat model

Featured Paper of the Month – May 2024

Xylazine, an increasingly abused drug mixed with fentanyl, leads to devastating respiratory issues during fentanyl-xylazine overdose. Despite naloxone being the primary treatment, it falls short in fully reversing the hypoxic effects of the drug mixture. Our study suggests that supplementing naloxone with atipamezole, a xylazine antagonist, provides a more effective and thorough solution for addressing brain hypoxia caused by fentanyl-xylazine mixture.

A linguistic analysis of dehumanization toward substance use across three decades of news articles

Featured Paper of the Month – April 2024

Published in Frontiers in Public Health by Salvatore Giorgi and Brenda Curtis, et al. of the NIDA IRP Technology and Translational Research Unit.

In this work, we apply a computational linguistic framework to measure dehumanization to 3 million news articles. We show that popular media in the U.S. has dehumanized people who used substances to varying degrees. Substances such as heroin have been strongly dehumanized for decades, while marijuana use is becoming less dehumanized over time, aligning with increased public support for legalization.

Brain Functional Connectome Defines a Transdiagnostic Dimension Shared by Cognitive Function and Psychopathology in Preadolescents

Featured Paper of the Month – March 2024
Published in Biological Psychiatry by Xiang Xiao and Yihong Yang, et al. of the NIDA IRP Magnetic Resonance Imaging and Spectroscopy Section.

Cognitive function and general psychopathology are two important classes of human behavior dimensions that are individually related to mental disorders across diagnostic categories. However, whether these two transdiagnostic dimensions are linked to common or distinct brain networks that convey resilience or risk for the development of psychiatric disorders remains unclear.

Alkoxy chain length governs the potency of 2-benzylbenzimidazole ‘nitazene’ opioids associated with human overdose

Featured Paper of the Month – February 2024
Published in Psychopharmacology by Grant Glatfelter and Michael Baumann et al. of the NIDA IRP Designer Drug Research Unit.

Our findings reveal that nitazenes are potent mu-opioid receptor agonists that induce opioid-like effects in mice. Importantly, we show that certain analogs (e.g., isotonitazene, etonitazene) are much more potent than fentanyl, portending serious risk of overdose and other adverse effects in humans who are exposed to the drugs.

Anterior hypothalamic parvalbumin neurons are glutamatergic and promote escape behavior

Featured Paper of the Month – January 2024
Published in Current Biology by Brenton Laing and Yeka Aponte, et al. of the NIDA IRP Neuronal Circuits and Behavior Section.

Using techniques including in vivo functional imaging, behavioral paradigms, and neuronal tracing, Laing et al. investigated a small population of parvalbumin neurons in the anterior hypothalamic area (AHA^PV).

Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D₃ (D₃R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics.

Featured Paper of the Month – December 2023
Published in Journal of Medicinal Chemistry by Alessandro Bonifazi , Lily Saab and Amy Hauck Newman of the NIDA IRP Medicinal Chemistry Section.

The Newman Lab published a new generation of dual-target mu opioid receptor (MOR) agonists/dopamine D3 receptor (D3R) antagonists/partial agonists as potentially safer analgesics.

Interactions of calmodulin kinase II with the dopamine transporter facilitate cocaine-induced enhancement of evoked dopamine release

Featured Paper of the Month – November 2023
Published in Translational Psychiatry by Jacqueline Keighron and Gianluigi Tanda, et al. of the NIDA IRP Medication Development Program.

In this study, we show that pretreatments with an inhibitor of CaMKIIα, a kinase that interacts with DAT and regulates synapsin phosphorylation and mobilization of reserve pools of DA vesicles, blunted the effects of cocaine on evoked DA release without affecting cocaine inhibition of DA reuptake.