Featured Paper of the Month

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…

Featured Paper of the Month – July 2021
Published in International Journal of Neuropsychopharmacology by  Mehdi Farokhnia and Lorenzo Leggio, et al. in the NIDA IRP Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section.

Evidence from preclinical and clinical studies suggest that the orexigenic hormone ghrelin modulates alcohol-seeking behaviors. Accordingly, the ghrelin system is being studied as a potential pharmacotherapeutic target for alcohol use disorder (AUD). Both ghrelin and alcohol interact with a variety of endocrine pathways, especially those related to appetite, metabolism, and stress. To better understand the complex interplay between ghrelin and other hormones in the context of alcohol use, the present study examined neuroendocrine response to a supraphysiological challenge with exogenous ghrelin, combined with alcohol, in a clinically relevant sample of heavy-drinking individuals with AUD…

Featured Paper of the Month – June 2021
Published in Communications Biology by  Christopher Cover and Hanbing Lu, et al. in the NIDA IRP Magnetic Resonance Imaging and Spectroscopy Section.

Functional magnetic resonance imaging (fMRI) can image brain dynamics while a human subject engages in a goal-directed task, it has proven extremely challenging to perform similar studies in rodents due to the difficulty in both limiting motion and mitigating stress during task performance. Herein we report a method that makes this possible: mice are cued to lick a spout to receive optogenetic stimulation. Noninvasive whole brain readout combined with circuit-specific neuromodulation opens an avenue for investigating adaptive behavior in both healthy and disease models…

Featured Paper of the Month – May 2021
Published in Psychopharmacology by  Leigh V Panlilio, et al. in the NIDA IRP Real-world Assessment, Prediction, and Treatment Unit.

Despite the popular conception that people in treatment for opioid addiction either become abstinent or relapse into a spiral of continuous drug use, many actually continue using drugs to some intermediate degree. Some use drugs frequently, some use sporadically, and some use very rarely. In this paper, we show that groups of people who share similar patterns of use also tend to be alike in other ways. For example, we find that those who use sporadically are unusual in that they do not seem to be driven by drug craving, but tend to use simply because they were offered drugs…

Featured Paper of the Month – April 2021
Published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging by  John Fedota, Ph.D. and Thomas Ross, Ph.D.,  et al. in the NIDA IRP Cognitive and Affective Neuroscience of Addiction Section.

Quitting smoking is hard. This is largely due to the nicotine withdrawal syndrome. Withdrawal from cigarettes is characterized by craving, bad feelings and losses of attention. Importantly, these negative symptoms are known to fluctuate wildly in time. Inspired by this, NIDA scientists applied a technique that allowed us to look at how communication across the entire brain fluctuated over time during smoking and withdrawal. Twenty-five smokers came to NIDA twice each. During the first visit they smoked a cigarette and were not in withdrawal. Before the second visit, they did not smoke for 2 days and so were in peak withdrawal. At each visit they underwent a function magnetic resonance imaging (MRI) scan…