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Intrinsic differences in insular circuits moderate the negative association between nicotine dependence and cingulate-striatal connectivity strength

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…

NIDA IRP Scientist Michael Baumann, Ph.D. Edits a Special Journal Issue on Opioid Pharmacology

The origins of the current opioid crisis are complex, and effective solutions will require multidisciplinary cooperation among many stakeholders, including policymakers, clinicians, and scientists. To this end, basic research in pharmacology can provide critical information for addressing the crisis. In a Special Issue of Neuropharmacology, entitled “New Vistas in Opioid Pharmacology”, Dr Michael Baumann from the… [Read More]

The Role of Peripheral Opioid Receptors in Triggering Heroin-induced Brain Hypoxia

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…

Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism.

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…

Cocaine-induced endocannabinoid signaling mediated by sigma-1 receptors and extracellular vesicle secretion.

Featured Paper of the Month – Apil 2020
Published in Elife by Nakamura, Yoki; Dryanovski, Dilyan I; Kimura, Yuriko; Jackson, Shelley N; Woods, Amina S; Yasui, Yuko; Tsai, Shang-Yi; Patel, Sachin; Covey, Daniel P; Su, Tsung-Ping; Lupica, Carl R

By studying brain tissue and neurons in vitro, Nakamura, Dryanovski et al. show that cocaine stimulates the release of endocannabinoids via extracellular vesicles. In essence, cocaine causes neurons to synthesize endocannabinoids that are then enclosed within membrane-bound packages. These packages – or extracellular vesicles – can then fuse with the cell’s membrane. Multiple protein interactions are necessary to permit this extracellular vesicle release, and the authors show that disrupting these control points prevents vesicle release…

Abstinence-dependent dissociable central amygdala microcircuits control drug craving

Hot Off the Press – March 27 , 2020. The current study offers a mechanistic explanation for the protective effect of social interaction on incubation of craving in rodents, showing that it is mediated by the activation of neurons expressing the enzyme PKCδ the brain’s amygdala. The study also shows that activation of a peptide… [Read More]

Advances in the science and treatment of alcohol use disorder.

Reviews To Read – March 2020. In this review, the authors critically report the scientific and clinical evidence supporting alcohol use disorder as a treatable disease using medications and/or behavioral treatments. Approved treatments and promising new interventions are reviewed and discussed, with a special emphasis on personal treatment approaches. The authors also note the critical… [Read More]

Dopamine neuron ensembles signal the content of sensory prediction errors

Featured Paper of the Month – March 2020
Published in Elife by Stalnaker, Thomas A; Howard, James D; Takahashi, Yuji K; Gershman, Samuel J; Kahnt, Thorsten; Schoenbaum, Geoffrey

Midbrain dopamine neurons have long been thought to collectively signal a value prediction error, indicating whether the value of an event is greater or less than expected. A few years ago, our lab showed that these neurons also signal if an event is different than expected, without regard for value. In this paper, we build on this prior result by showing in both rats and humans that dopamine neurons or midbrain BOLD voxels, as a group, signal which unexpected event has occurred…

Cannabidiol: Not a Cure-All, but a Candidate for Coping With Cue-Induced Craving

Reviews To Read – February 2020. In this commentary, David Epstein evaluates a recent human-laboratory study that showed promising results for cannabidiol (CBD) as an anti-craving medication in people with recent histories of opioid use disorder (OUD). He emphasizes that people at different stages of opioid use or OUD have different needs, so potential treatments… [Read More]

Eliot Gardner Wins WCBR Pioneer Award

The Winter Conference on Brain Research (WCBR) has presented Eliot Gardner, Ph.D. of the NIDA IRP with the Pioneer Award for his lifetime of work in the field of neuropsychopharmacology. Dr. Gardner has attended WCBR for more than 50 years , participating in countless panels and workshops. He has also brought many of his students… [Read More]