Featured Paper of the Month

Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D₃ (D₃R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics.

Featured Paper of the Month – October 2023
Published in Drug and Alcohol Dependence with contributions from Michael Baumann and colleagues from the NIDA IRP.

For this study, we examined the pharmacological effects of non-fentanyl synthetic opioids, including U-47700, brorphine, and isotonitazene, as compared to morphine and fentanyl.

Interactions of calmodulin kinase II with the dopamine transporter facilitate cocaine-induced enhancement of evoked dopamine release

Featured Paper of the Month – October 2023
Published in Drug and Alcohol Dependence with contributions from Michael Baumann and colleagues from the NIDA IRP.

For this study, we examined the pharmacological effects of non-fentanyl synthetic opioids, including U-47700, brorphine, and isotonitazene, as compared to morphine and fentanyl.

Comparative neuropharmacology of structurally distinct non-fentanyl opioids that are appearing on recreational drug markets worldwide

Featured Paper of the Month – October 2023
Published in Drug and Alcohol Dependence with contributions from Michael Baumann and colleagues from the NIDA IRP.

For this study, we examined the pharmacological effects of non-fentanyl synthetic opioids, including U-47700, brorphine, and isotonitazene, as compared to morphine and fentanyl.

Inhibition of dorsal raphe GABAergic neurons blocks hyperalgesia during heroin withdrawal

Featured Paper of the Month – September 2023
Published in Neuropsychopharmacology by Yocasta Alvarez-Bagnarol, and Marisela Morales, et al. of the NIDA IRP Neuronal Networks Section.

We demonstrated that inhibition of Dorsal Raphe GABA neurons blocks hyperalgesia (increased pain sensitivity) induced by spontaneous heroin withdrawal.

Waving Through the Window: A Model of Volitional Social Interaction in Female Mice.

Featured Paper of the Month – August 2023
Published in Biological Psychiatry by Leslie Ramsey, and Marco Venniro, et al. of the NIDA IRP Neurobiology of Relapse Section.

Using a battery of behavioral tests, we demonstrated that female CD1 mice find social interaction more rewarding compared to female C57BL/6J mice. Our data show that CD1 mice are a better strain for studying female social reward learning.

Dopamine D₃/D₂ Receptor Ligands Based on Cariprazine for the Treatment of Psychostimulant Use Disorders That May Be Dual Diagnosed with Affective Disorders

Featured Paper of the Month – July 2023
Published in The Journal of Medicinal Chemistry by Emma Gogarnoiu, Caleb Vogt and Amy Hauck Newman, et al. of the NIDA IRP Medicinal Chemistry Section.

Cocaine and methamphetamine are highly addictive psychostimulants that continue to challenge the health and well-being of those who develop a psychostimulant use disorder (PSUD). To date, there are no FDA approved medications for the treatment of PSUD and this provides a significant challenge to curb its destructive nature and prevent death by overdose.

Mu Opioid Receptor Activation Mediates (S)-ketamine Reinforcement in Rats: Implications for Abuse Liability

Featured Paper of the Month – June 2023
Published in Biological Psychiatry by Marjorie Levinstein and Michael Michaelides, et al. of the NIDA IRP Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit.

In this study, we show that S-ketamine not only binds to and activates MOR, but that this interaction is critical for its abuse liability. Specifically, we show that the opioid receptor antagonist naltrexone blocks brain activation by (S)-ketamine in the nucleus accumbens, a region crucial for reward, and also decreases lever pressing for (S)-ketamine in rats.

Persistent binding at dopamine transporters determines sustained psychostimulant effects

Featured Paper of the Month – May 2023
Published in PNAS with contributions from Carl Lupica, Alexander Hoffman, and Michael Baumann of the NIDA IRP.

Here we demonstrate that various DAT inhibitors can be distinguished based on their in vitro binding kinetics, whereby the dissociation rate (i.e., Koff) of a drug from DAT in vitro predicts the duration of its stimulant effects in vivo.

The SARS-CoV-2 spike protein binds and modulates estrogen receptors

Featured Paper of the Month – April 2023
Published in Science Advances by Oscar Solís and Michael Michaelides et al. from the NIDA IRP Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit.

In our study, we investigated the potential impact of the spike protein of the SARS-CoV-2 virus on estrogen receptors. To do so, we used computational and biochemical methods to study the binding of the spike protein to human estrogen receptors…

Compulsive drug-taking is associated with habenula-frontal cortex connectivity

Featured Paper of the Month – March 2023
Published in PNAS by Ying Duan, Pei-Jung Tsai and Yihong Yang, et al. from the NIDA IRP Magnetic Resonance Imaging and Spectroscopy Section.

Compulsive drug use, as the defining feature of substance use disorder, is attributed to disadvantageous decision-making and has been associated with dysfunction of frontal-midbrain systems. The habenula is a relay node between forebrain and midbrain regions and processes negative feedback in response to aversive events. To understand the contributions of frontal-habenula-midbrain circuits in the development of drug dependence, we employed a rat model of methamphetamine self-administration in the presence of concomitant footshock, which has been proposed to model compulsive drug-taking in humans…