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Distinct prelimbic cortex ensembles encode response execution and inhibition.

Featured Paper of the Month – January 2026
Published in PNAS by Rajtarun Madangopal, Ph.D. and Bruce Hope, Ph.D. of the NIDA IRP Neuronal Ensembles in Drug Addiction Section.

In this study, researchers used single-cell calcium imaging to longitudinally track hundreds of brain cells (neurons) in rats across three phases: when they pressed a lever for food rewards (Training), as they learned to stop pressing when the reward was removed (Extinction), and when they resumed pressing after a small, non-contingent reward was reintroduced (Reinstatement). Analyses showed that distinct and non-overlapping populations – called ensembles – were active during Training and Extinction, to support response execution and inhibition, respectively.

A novel atypical DAT inhibitor that inhibits cocaine taking and seeking and itself has low abuse potential in experimental animals.

Featured Paper of the Month – December 2025
Published in Translational Psychiatry by Omar Soler-Cedeño and Zheng-Xiong Xi, M.D., Ph.D. of the NIDA IRP Addiction Biology Unit.

This study evaluated two new compounds in animal models: RDS-04-010, an atypical dopamine transporter (DAT) inhibitor that binds to an inward-facing conformation of DAT, and RDS-03-094, a more typical DAT inhibitor that binds to an outward-facing conformation. Notably, RDS-04-010 reduced cocaine use, lowered motivation to seek cocaine, and prevented relapse-like behavior, while showing no rewarding or addictive effects on its own. These findings highlight RDS-04-010 as a promising treatment candidate.

Brain reactivity to nicotine cues mediates the link between resting-state connectivity and cue-induced craving in individuals who smoke or vape nicotine

Featured Paper of the Month – November 2025
Published in Neuropsychopharmacology by Laura Murray and Amy Janes of the NIDA IRP Cognitive and Pharmacological Neuroimaging Section.

This project tested whether brain and subjective responses to nicotine cues differed between individuals who smoke versus vape nicotine, and whether brain function at rest was related to how the brain responded to nicotine cues and how exposure to nicotine cues influences subjective craving.

Characterizing Olfactory Brain Responses in Young Infants

Featured Paper of the Month – October 2025
Published in The Journal of Neuroscience by Thorsten Kahnt of the NIDA IRP Learning and Decision-Making Section.

In this study, we presented different odors to sleeping infants while recording their nasal airflow and brain activity using functional magnetic resonance imaging (fMRI). Odors evoked strong fMRI responses throughout the olfactory cortex and thalamus. Moreover, analysis of nasal airflow showed that infants inhaled more strongly to pleasant compared to unpleasant odors, suggesting they may adjust their breathing based on odor preference.

Technology Resource Initiative – Paper of the Month – September 2025

Astrocytes modulate cerebral blood flow and neuronal response to cocaine in prefrontal cortex Mol Psychiatry.

This study introduces a novel multi-channel fluorescence and ultra high-resolution optical coherence Doppler microscope (fl-ODM) that enables simultaneous in vivo imaging of neuronal, astrocytic, and vascular dynamics in the mouse brain. Using this tool, the research uncovers how astrocytes dynamically regulate cocaine-induced changes in cerebral blood flow and neuronal activation in the prefrontal cortex.

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Serotonin 1A Receptors Modulate Serotonin 2A Receptor-Mediated Behavioral Effects of 5-Methoxy-,-dimethyltryptamine Analogs in Mice

Featured Paper of the Month – September 2025
Published in ACS Chemica Neuroscience by Grant Glatfelter and Michael Baumann of the NIDA IRP Designer Drug Research Unit.

In this study, we show that 5-MeO-DMT and related analogs potently activate 5-HT1A receptors, which tend to decrease the magnitude of 5-HT2A-mediated behavioral effects in mice.

Hippocampal output suppresses orbitofrontal cortex schema cell formation

Hot Off the Press – August 21, 2025 Published in Nature Neuroscience by Wenhui Zong and Geoffrey Schoenbaum, et al. of the NIDA IRP Behavioral Neurophysiology Neuroscience Section. Summary The orbitofrontal cortex (OFC) and hippocampus (HC) are both thought to contribute to the construction of cognitive maps and their generalization into schemas, yet the nature… [Read More]

Technology Resource Initiative – Paper of the Month – August 2025

Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states. Published in Science.

Understanding how psychedelics exert therapeutic effects without inducing hallucinogenic side effects is a key challenge in neuropsychiatric drug development. Muir et al. combine multiple cutting-edge neuroscience approaches to dissociate the neural mechanisms underlying the anxiolytic-like and hallucinogenic-like effects of the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI). They identify a population of DOI-responsive neurons in the medial prefrontal cortex that mediate anxiolytic-like effects without inducing hallucinogenic-like behaviors, paving the way for the development of more targeted psychedelic therapies.

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Locomotor activity depends on β-arrestin recruitment by the dopamine D₁ receptor in the striatal D₁-D₃ receptor heteromer

Hot Off the Press – August, 2025 Published in Pharmacological Research by Alexandra Evans and Sergi Ferré , et al. of the NIDA IRP Integrative Neurobiology Section. Summary It has been long advocated that the mechanism responsible for the classically established cooperative effect of dopamine D1-like and D2-like receptor agonists in the elicitation of locomotor activity… [Read More]

The Role of Claustrum in Incubation of Opioid Seeking after Electric Barrier-Induced Voluntary Abstinence in Male and Female Rats

Featured Paper of the Month – August 2025
Published in Journal of Neuroscience by Kenichiro Negishi, Ying Duan, Yihong Yang, Yavin Shaham and Ida Fredriksson, et al. of the NIDA IRP Magnetic Resonance Imaging and Spectroscopy Section and Neurobiology of Relapse Section.

In the present study, we used immunohistochemistry, anatomical tracing, and reversible inactivation methods to identify a critical role of a brain region called the claustrum and its anatomical connections with ventral subiculum in incubation of oxycodone seeking.