Featured Paper of the Month

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…

Featured Paper of the Month – September 2020
Published in Nature Communications by Plenge, Per; Abramyan, Ara M; Sørensen, Gunnar; Mørk, Arne; Weikop, Pia; Gether, Ulrik; Bang-Andersen, Benny; Shi, Lei; Loland, Claus J

The serotonin transporter (SERT) terminates serotonin signaling by rapid presynaptic reuptake. SERT activity is modulated by antidepressants, e.g., S-citalopram and imipramine, to alleviate symptoms of depression and anxiety. SERT crystal structures reveal two S-citalopram binding pockets in the central binding (S1) site and the extracellular vestibule (S2 site). In this study, our combined in vitro and in silico analysis indicates that the bound S-citalopram or imipramine in S1 is allosterically coupled to the ligand binding to S2 through altering protein conformations…

Featured Paper of the Month – August 2020
Published in Journal of Neuroscience by Reiner, David J; Lofaro, Olivia M; Applebey, Sarah V; Korah, Hannah; Venniro, Marco; Cifani, Carlo; Bossert, Jennifer M; Shaham, Yavin

Fentanyl is a major contributor to the opioid overdose crisis, but there are few preclinical studies of fentanyl relapse. These studies have used experimenter-imposed extinction or forced abstinence procedures. In humans, however, abstinence is often voluntary, with drug available in the drug environment but forgone in favor of nondrug alternative reinforcers. We recently developed a rat model of drug relapse after palatable food choice-induced voluntary abstinence. Here, we used classical pharmacology, immunohistochemistry, and retrograde tracing to demonstrate a critical role of the piriform and orbitofrontal cortices in relapse to fentanyl seeking after voluntary abstinence…

Featured Paper of the Month – July 2020
Published in Neuropsychopharmacology by Keeley, Robin J; Hsu, Li-Ming; Brynildsen, Julia K; Lu, Hanbing; Yang, Yihong; Stein, Elliot A

Developing brain-based biomarkers to assess drug dependence, including nicotine dependence, are essential to assess and improve the current, marginally effective, treatments. In humans, using brain-based resting state functional connectivity, we have previously identified a circuit between the dorsal anterior cingulate cortex(ACC) and the striatum whose connectivity decreased with increasing nicotine dependence severity. This circuit was unaffected by acute nicotine administration, suggesting a trait marker of nicotine addiction. However, whether this trait circuit dysregulation is predispositional or resultant from nicotine dependence remained unclear…