News Main

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…

Featured Paper of the Month – June 2020
Published in Sci Rep by Perekopskiy, David; Afzal, Anum; Jackson, Shelley N; Muller, Ludovic; Woods, Amina S; Kiyatkin, Eugene A

One of the deadliest effects of opioids, such as heroin, is respiratory depression followed by brain hypoxia. While it is known that opioid receptors are densely expressed in both the brain and periphery, it is widely accepted that the hypoxic effects of opioids result solely from their direct action in the CNS. To examine the role of peripheral opioid receptors in triggering brain hypoxia, we used oxygen sensors in freely moving rats to examine how naloxone-HCl and naloxone-methiodide affect brain oxygen responses induced by intravenous heroin at low, human-relevant doses…

Featured Paper of the Month – May 2020
Published in Elife by Lane, Robert J; Abramyan, Ara M; Adhikari, Pramisha; Keen, Alastair C; Lee, Kuo-Hao; Sanchez, Julie; Verma, Ravi Kumar; Lim, Herman D; Yano, Hideaki; Javitch, Jonathan A; Shi, Lei

Lane et al. proposed that different types of antagonists could prefer specific types of inactive conformations of the dopamine D₂ and D₃ receptors. Based on the structures of these two receptors, the conformations of D₂ bound with the drugs risperidone and eticlopride (two dopamine antagonists) were simulated and compared. The results show that the inactive conformations of D₂ were very different when it was bound to eticlopride as opposed to risperidone…