Featured Paper of the Month

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…

Featured Paper of the Month – March 2021
Published in The Journal of Neuroscience by  Ewa Galaj, Ph.D. Ph.D. and Zheng-Xiong Xi, M.D., Ph.D.,  et al. in the NIDA IRP Addiction Biology Unit.

Opioid reward has long been believed to be mediated by inhibition of VTA GABA interneurons that disinhibits DA neurons. In this study, we found that  GABA neurons of the neighboring substantia nigra pars reticulata play a more important role in opioid reward and relapse than VTA GABA interneurons…

Featured Paper of the Month – February 2021
Published in ACS Chemical Neuroscience by Guthrie, Daryl A; Herenbrink, Carmen Klein; Lycas, Matthew Domenic; Ku, Therese; Bonifazi, Alessandro; DeVree, Brian T; Mathiasen, Signe; Javitch, Jonathan A; Grimm, Jonathan B; Lavis, Luke; Gether, Ulrik; Newman, Amy Hauck

The dopamine transporter (DAT) functions to control dopaminergic neurotransmission and is a target for therapeutic agents, including ADHD medications, as well as abused substances, such as cocaine. Here, we develop new fluorescently labeled ligands as promising new tools for studying DAT localization and regulation with single-molecule resolution…

Featured Paper of the Month – January 2021
Published in Archives of Toxicology by Subu, Rajeev; Jayanthi, Subramaniam; Cadet, Jean Lud

The use of  methamphetamine (METH) is very prevalent throughout the world. METH can cause anxiety, psychosis, seizures, and death. Previous research in the Cadet Lab has shown that METH can cause neurodegeneration when the drug is injected by investigators.  It was therefore important to find out if there is degeneration in the brains of rats that learn to give themselves METH by a behavioral technique called self-administration (SA)…

Featured Paper of the Month – December 2020
Published in ACS Medicinal Chemistry Letters by Battiti, Francisco O; Newman, Amy Hauck; Bonifazi, Alessandro

In this study, starting from our highly selective and potent D3R agonist 5 , we further investigated the chemical space around the linker portion of the molecule, via insertion of a hydroxyl substituent and ring-expansion of the trans cyclopropyl moiety into a trans -cyclohexyl scaffold…

Featured Paper of the Month – November 2020
Published in ACS Chemical Neuroscience in Yano, Hideaki; Adhikari, Pramisha; Naing, Sett; Hoffman, Alexander F; Baumann, Michael H; Lupica, Carl R; Shi, Lei

The nonmedical (i.e., recreational) misuse of synthetic cannabinoids (SCs) is a worldwide public health problem. When compared to cannabis, the misuse of SCs is associated with a higher incidence of serious adverse effects, suggesting the possible involvement of noncannabinoid sites of action. Here, we find that, unlike the phytocannabinoid Δ⁹-tetrahydrocannabinol, the indole-moiety containing SCs, AM2201 and JWH-018, act as positive allosteric modulators (PAMs) at the 5-HT_1A receptor (5-HT_1AR). This suggests that some biological effects of SCs might involve allosteric interactions with 5-HT_1ARs…

Featured Paper of the Month – October 2020
Published in Neuropsychopharmacology by Mereu, Maddalena; Hiranita, Takato; Jordan, Chloe J; Chun, Lauren E; Lopez, Jessica P; Coggiano, Mark A; Quarterman, Juliana C; Bi, Guo-Hua; Keighron, Jacqueline D; Xi, Zheng-Xiong; Newman, Amy Hauck; Katz, Jonathan L; Tanda, Gianluigi

Modafinil and methylphenidate are clinically available medications that inhibit the reuptake of dopamine in neurons, a common mechanism with psychostimulants like cocaine. We investigated the reinforcing actions of modafinil or methylphenidate alone and in combination with cocaine, in rats. While rats did not self-administer modafinil, suggesting low abuse liability, methylphenidate was self-administered similarly to cocaine. However, while both drugs potentiated cocaine’s reinforcing effects, only methylphenidate potentiated the elevated dopamine levels produced by cocaine…