Article
Biochemistry & Molecular Biology
Soichiro Ide, Noriaki Iwase, Kenichi Arai, Masahiro Kojima, Shigeru Ushiyama, Kaori Taniko, Kazutaka Ikeda
Summary: Despite the widespread use of opioids for pain management, opioid addiction and the overdose crisis are becoming increasingly serious. A new nonpeptide ligand, UD-030, has been found to be a selective mu-opioid receptor antagonist and shows promise as a treatment option for opioid use disorder, with different characteristics from traditional medications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Psychiatry
Javier Ballester, Anne K. Baker, Ilkka K. Martikainen, Vincent Koppelmans, Jon-Kar Zubieta, Tiffany M. Love
Summary: This study found that chronic pain patients at high risk for opioid misuse showed higher baseline MOR availability in the right amygdala, while patients at low risk for opioid misuse showed less pain-induced activation of MOR-mediated, endogenous opioid neurotransmission in the nucleus accumbens.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Cell Biology
Wei Wang, Xueyi Xie, Xiaowen Zhuang, Yufei Huang, Tao Tan, Himanshu Gangal, Zhenbo Huang, William Purvines, Xuehua Wang, Alexander Stefanov, Ruifeng Chen, Lucas Rodriggs, Anita Chaiprasert, Emily Yu, Valerie Vierkant, Michelle Hook, Yun Huang, Emmanuel Darcq, Jun Wang
Summary: Withdrawal from chronic opioid use leads to hypodopaminergic states and negative affect, promoting relapse. Activation of MORs in dMSNs in the striatal patch compartment suppresses striatopallidal transmission, and withdrawal potentiated this transmission. Fentanyl self-administration enhances striatonigral transmission and reduces dopaminergic activity, while activated striatal neurons mediate contextual memory retrieval. Inhibition of striatal MOR+ neurons rescues fentanyl withdrawal-induced physical symptoms and anxiety-like behaviors. These findings suggest that chronic opioid use induces GABAergic striatopallidal and striatonigral plasticity, leading to hypodopaminergic states and relapse.
Review
Pharmacology & Pharmacy
Charles P. France, Gerard P. Ahern, Saadyah Averick, Alex Disney, Heather A. Enright, Babak Esmaeli-Azad, Arianna Federico, Lisa R. Gerak, Stephen M. Husbands, Benedict Kolber, Edmond Y. Lau, Victoria Lao, David R. Maguire, Michael A. Malfatti, Girardo Martinez, Brian P. Mayer, Marco Pravetoni, Niaz Sahibzada, Phil Skolnick, Evan Y. Snyder, Nestor Tomycz, Carlos A. Valdez, Jim Zapf
Summary: The only medication available to prevent and treat opioid overdose is naloxone, approved by the FDA nearly 50 years ago. Due to its limitations, a scientific meeting was convened by NIAID/NIH to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. This meeting discussed new approaches such as intranasal nalmefene, methocinnamox, covalent naloxone nanoparticles, serotonin receptor agonists, fentanyl-binding cyclodextrin scaffolds, detoxifying biomimetic nanosponge decoy receptors, and antibody-based strategies.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Vishakh Iyer, Claudia Rangel-Barajas, Taylor J. Woodward, Abhijit Kulkarni, Lucas Cantwell, Jonathon D. Crystal, Ken Mackie, George V. Rebec, Ganesh A. Thakur, Andrea G. Hohmann
Summary: Researchers have developed a novel drug candidate that can block the rewarding effects of opioid drugs by attenuating the signaling of cannabinoid type 1 (CB1) receptors. This drug works by decreasing the affinity and/or efficacy of CB1 ligands. The results show that this drug could potentially be used to prevent opioid reward and treat opioid abuse without unwanted side effects.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Gary B. Kaplan, Benjamin L. Thompson
Summary: Opioid use disorder is characterized by excessive use of opioids, inability to control use, withdrawal syndrome, and likelihood of relapse. The opponent process view of motivation suggests that opioid addiction involves positive affective experiences during active involvement and negative affective experiences during abstinence. These negative experiences are hypothesized to be caused by neuroadaptations in the extended amygdala, which includes the CeA, BNST, and NAc shell, as well as input from the BLA. Animal models of opioid withdrawal demonstrate the somatic, motivational, affective, and learning related aspects of withdrawal. Neuroadaptations in the extended amygdala lead to aversive and fear-related effects, hypodopaminergia, and increased vulnerability to relapse. Understanding and reversing these neuroadaptations could lead to new interventions for opioid use disorder.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Soichiro Ide, Hirofumi Kunitomo, Yuichi Iino, Kazutaka Ikeda
Summary: Addiction is a significant global societal problem, but effective treatments are limited. The nematode Caenorhabditis elegans is a valuable invertebrate model for studying neurobiological diseases and has shown preference for cues associated with addictive drugs. Recent studies have discovered an opioid-like system in C. elegans. This study found that C. elegans exhibited dose-dependent preference for morphine and aversion to naloxone-precipitated withdrawal, indicating the presence of an addictive function of the opioid system in C. elegans.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Darrell Eacret, Crystal Lemchi, Jasmine I. Caulfield, Sonia A. Cavigelli, Sigrid C. Veasey, Julie A. Blendy
Summary: This study investigates the influence of chronic short sleep on opioid reward using a mouse model. The results show that recovery sleep after chronic sleep disruption lessens voluntary opioid intake, but does not affect conditioned reward associated with morphine.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Xiaodan Li, Jian Xiong, Baojian Zhang, Dongting Zhangsun, Sulan Luo
Summary: Morphine, a common analgesic, has limited clinical application due to abuse potential. Nicotinic acetylcholine receptors (nAChRs) in the brain play a key role in drug addiction. The study discovered a selective ligand, alpha-Conotoxin TxIB, which inhibits a specific type of nAChRs and may be useful in mitigating drug addiction.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Pablo Berrios-Carcamo, Mauricio Quezada, Daniela Santapau, Paola Morales, Belen Olivares, Carolina Ponce, Alba avila, Cristian De Gregorio, Marcelo Ezquer, Maria Elena Quintanilla, Mario Herrera-Marschitz, Yedy Israel, Fernando Ezquer
Summary: The study establishes a voluntary oral morphine consumption animal model by training rats to accept a bitter taste preference, which can be used to evaluate therapeutic interventions for the treatment of morphine dependence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Giorgia Caspani, Viktoria Sebok, Nowshin Sultana, Jonathan R. Swann, Alexis Bailey
Summary: Metabolomics can elucidate the biochemical impact of substance abuse, understand the addiction cycle, and predict prognosis for recovery or relapse.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Julong Wei, Tova Y. Lambert, Aditi Valada, Nikhil Patel, Kellie Walker, Jayna Lenders, Carl J. Schmidt, Marina Iskhakova, Adnan Alazizi, Henriette Mair-Meijers, Deborah C. Mash, Francesca Luca, Roger Pique-Regi, Michael J. Bannon, Schahram Akbarian
Summary: This study found that chronic exposure to opioids results in broad transcriptional changes in glial cells, including upregulation of genes associated with immune response and downregulation of synaptic signaling and plasticity genes. It also identified certain genes that are linked to risk of substance use in the population.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Siroshini K. Thiagarajan, Siew Ying Mok, Satoshi Ogawa, Ishwar S. Parhar, Pek Yee Tang
Summary: This study used zebrafish larvae as a model to investigate the effects of dopamine receptor antagonists and morphine on social behavior and locomotion. The levels of dopamine and the number of dopaminergic neurons were measured, and gene expression analysis revealed changes associated with schizophrenia. Termination of morphine use also led to changes in gene expression. The integrated data suggest that the dopamine system plays a key role in the schizophrenia-like symptoms and opioid dependence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Ariel T. Amgott-Kwan, James E. Zadina
Summary: Currently available mu-opioid receptor agonist pharmacotherapies for opioid use disorder have limited use due to adverse effects and high rates of relapse. However, a study found that the endomorphin analog ZH853 showed no abuse liability in rodent models and could potentially be used for managing opioid use disorder. The study demonstrated that ZH853 did not induce locomotor activation in male and female mice and was not self-administered by female rats. It also showed that ZH853 had lower abuse liability compared to morphine and could extinguish opioid-seeking behavior in male rats. Overall, these findings suggest the potential use of ZH853 as a safer opioid medication for long-term treatment of pain and opioid use disorder.
Article
Multidisciplinary Sciences
Sarah Stevens, Shekher Mohan
Summary: With the increasing opioid use among pregnant women and the resulting rise in infants born with neonatal opioid withdrawal syndrome (NOWS), there is a need to understand the short and long-term effects of prenatal opioid exposure. The study using spiny mice as a model found that prenatal morphine exposure led to increased withdrawal behavior in early postnatal period, indicating the potential for this species as a novel preclinical model of NOWS.
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.