Review
Biochemistry & Molecular Biology
Yu Liu, Gavan P. McNally
Summary: Dopamine plays a crucial role in relapse to drug seeking, with different forms of relapse being driven by distinct dopamine mechanisms. Understanding the diverse dopamine pathways involved in relapse behaviors is essential for developing effective strategies to prevent relapse.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Qingxiao Hong, Wenjin Xu, Zi Lin, Jing Liu, Weisheng Chen, Huaqiang Zhu, Miaojun Lai, Dingding Zhuang, Zemin Xu, Dan Fu, Wenhua Zhou, Huifen Liu
Summary: Epigenetic modifications, such as DNA methylation, play a crucial role in regulating gene expression and may influence neuroplasticity and drug-induced aberrant behaviors. The study in Sprague-Dawley rats showed that heroin self-administration led to hypomethylation of the GABRD gene and transcriptional upregulation in the NAc. Manipulations with DNMT inhibitor and MET affected heroin-seeking behavior, possibly through direct repression of DNMT1 and DNMT3A expression to alter the DNA methylation landscape of the GABRD gene.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Amy Chan, Alexis Willard, Sarah Mulloy, Noor Ibrahim, Allegra Sciaccotta, Mark Schonfeld, Sade M. Spencer
Summary: This study investigated the potential therapeutic effects of metformin on cue-induced reinstatement of cocaine seeking. The results showed that metformin microinjected in the nucleus accumbens core attenuated cue-induced reinstatement in male and female rats. However, caution is warranted given the potential for metformin's effects to generalize to a natural reward in female rats.
Article
Multidisciplinary Sciences
Mary Tresa Zanda, Gabriele Floris, Stephanie E. Sillivan
Summary: This study found that the dosage of drugs and discriminative drug cues have different effects on the incubation of opioid craving, while the drug intake history also plays a role in the time-dependent drug-seeking.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Benjamin M. Siemsen, Sarah M. Barry, Kelsey M. Vollmer, Lisa M. Green, Ashley G. Brock, Annaka M. Westphal, Raven A. King, Derek M. DeVries, James M. Otis, Christopher W. Cowan, Michael D. Scofield
Summary: This study identified and characterized a specific subpopulation of nucleus accumbens neurons that receive dense prelimbic cortical input. These neurons play a crucial role in regulating cue-induced cocaine seeking behavior, but not sucrose seeking. Additionally, they undergo morphological changes during the peak of cocaine seeking. These findings provide insights into the neural mechanisms of drug relapse and offer a novel target for addiction therapeutics.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Chemistry, Physical
Hongsong Feng, Kaifu Gao, Dong Chen, Li Shen, Alfred J. Robison, Edmund Ellsworth, Guo-Wei Wei
Summary: This study utilizes machine learning and deep learning methods to analyze the interaction networks of dopamine, serotonin, and norepinephrine transporters and builds predictive models to assess drug repurposing potential and potential side effects for the treatment of cocaine addiction. Additionally, the study screens the absorption, distribution, metabolism, excretion, and toxicity properties of the drugs to identify potential leads for developing treatments.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Neurosciences
Rebecca S. Hofford, Tanner J. Euston, Rashaun S. Wilson, Katherine R. Meckel, Emily G. Peck, Arthur Godino, Joseph A. Landry, Erin S. Calipari, TuKiet T. Lam, Drew D. Kiraly
Summary: The research shows that G-CSF can accelerate cocaine extinction and reduce cue-induced cocaine seeking during abstinence by regulating proteins related to synapse and glutamate signaling in the mPFC. These findings suggest that G-CSF may serve as a research target to reduce drug craving or seeking behaviors, and its FDA-approved status could facilitate clinical translation swiftly.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Jason Yuen, Abhinav Goyal, Aaron E. Rusheen, Abbas Z. Kouzani, Michael Berk, Jee Hyun Kim, Susannah J. Tye, Charles D. Blaha, Kevin E. Bennet, Dong-Pyo Jang, Kendall H. Lee, Hojin Shin, Yoonbae Oh
Summary: For over 40 years, in vivo microdialysis techniques have been crucial in studying the effects of illicit substances on dopamine levels in the brain, but limitations have led to the development of a new electrochemical method known as M-CSWV. This method provides faster recordings of dopamine level changes, allowing for a more detailed understanding of neuronal responses to drug administration.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Man-yi Jing, Xiao-yan Ding, Xiao Han, Tai-yun Zhao, Min-min Luo, Ning Wu, Jin Li, Rui Song
Summary: This study found that cue-induced reinstatement of reward seeking is partially mediated by activation of the dopaminergic pathway from the VTA to the NAcore. In a mouse model, activation of this pathway triggered reinstatement of drug-seeking behavior, while inhibition of this pathway suppressed reinstatement behavior.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Myrto Panopoulou, Oliver M. Schlueter
Summary: Frequent relapse hinders successful treatment of substance use disorders by triggering the retrieval of drug-associated memories. This study investigates the cellular and molecular mechanisms underlying drug-induced memory retrieval using a conditioned place preference (CPP) procedure in mice. The results suggest that Ca2+-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc) play a key role in regulating the threshold for drug-induced retrieval and behavioral expression of drug memories.
MOLECULAR PSYCHIATRY
(2022)
Review
Pharmacology & Pharmacy
Celine Nicolas, Natalie E. Zlebnik, Mehdi Farokhnia, Lorenzo Leggio, Satoshi Ikemoto, Yavin Shaham
Summary: This review suggests that there may not necessarily be a gender difference in vulnerability to psychostimulant and opioid craving and relapse, although imaging studies indicate potential sex differences in brain responses to drug cues and stress. Preclinical studies show evidence for sex differences in cocaine seeking reinstatement and incubation, but not in methamphetamine or opioid seeking reinstatement or incubation.
PHARMACOLOGICAL REVIEWS
(2022)
Article
Neurosciences
Kelle E. Nett, Alexa R. Zimbelman, Matthew S. McGregor, Vanessa Alizo Vera, Molly R. Harris, Ryan T. LaLumiere
Summary: Previous evidence suggests that the infralimbic cortex (IL) plays a role in inhibiting cocaine seeking behavior in rats. In this study, the researchers investigated whether IL activity and its outputs to the nucleus accumbens shell (NAshell) and amygdala are involved in encoding extinction contingencies following cocaine self-administration. They used optogenetic techniques to silence IL-NAshell or IL-amygdala activity after an unreinforced lever press during extinction training and found that inhibition of IL-NAshell or IL-amygdala activity impaired extinction retention.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Nicholas A. Everett, Anita J. Turner, Priscila A. Costa, Sarah J. Baracz, Jennifer L. Cornish
Summary: The study found that peripherally administered oxytocin has inhibitory effects on METH self-administration and reinstatement, with a requirement for vagus nerve signaling involvement, and that this vagal dependency is partially mediated by sex and drug withdrawal.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Biology
Ruud van Zessen, Yue Li, Lucile Marion-Poll, Nicolas Hulo, Jerome Flakowski, Christian Luscher
Summary: LS is an early behavioral adaptation to addictive drugs, driven by increased dopamine in the NAc. During cocaine LS, D1R SPN activity increases while D2R SPN activity decreases, with a higher number of neurons responding in opposite directions. Inhibition of the ERK signaling pathway reduces the number of cocaine responsive D1R SPNs, indicating a dynamic dichotomy in accumbal population activity.
Article
Neurosciences
Tong-Yu Liang, Hua Zhou, Yan-Gang Sun
Summary: Ventral tegmental area (VTA) dopaminergic neurons participate in itch processing through their projection to the nucleus accumbens (NAc). The roles of dopamine receptor subtypes in different subregions of the NAc during itch processing were investigated. It was found that dopamine D1 receptors (D1R) blockade in the lateral shell (LaSh) impaired pruritogen-induced scratching behavior, while D2R activation in both LaSh and medial shell (MeSh) attenuated scratching behavior. Dopamine release in LaSh was elevated during scratching behavior, suggesting a motivational component of itch processing. This study highlights the importance of D1R in the LaSh of the NAc in itch signal processing.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cardiac & Cardiovascular Systems
Ying Wang, Qian Shi, Minghui Li, Meimi Zhao, Raghavender Reddy Gopireddy, Jian-Peng Teoh, Bing Xu, Chaoqun Zhu, Kyle E. Ireton, Sanghavi Srinivasan, Shaoliang Chen, Paul J. Gasser, Julie Bossuyt, Johannes W. Hell, Donald M. Bers, Yang K. Xiang
Summary: The study revealed the presence of a pool of beta(1)AR associated with the SR in mouse hearts, which play a critical role in PKA-mediated phosphorylation of phospholamban and cardiac contractility. Activation of these intracellular beta(1)ARs relies on catecholamine transport via OCT3.
CIRCULATION RESEARCH
(2021)
Article
Microbiology
Stephanie D. Nofal, Avnish Patel, Michael J. Blackman, Christian Flueck, David A. Baker
Summary: Guanylyl cyclases synthesize cyclic GMP, which plays a critical role in regulating cellular functions. In malaria parasites, GCs are associated with a unique bifunctional domain. The study shows that Plasmodium falciparum GC alpha is essential for cGMP production and merozoite egress, with the P4-ATPase domain playing a primary role in cGMP synthesis.
Review
Biochemistry & Molecular Biology
Aaron Caccamise, Erik Van Newenhizen, John R. Mantsch
Summary: Stress plays a critical role in relapse susceptibility in individuals with substance use disorders, either directly triggering cocaine use or interacting with other stimuli to promote drug seeking behavior. The mechanisms of stress-triggered cocaine seeking involve various neural pathways and hormonal regulations.
JOURNAL OF NEUROCHEMISTRY
(2021)
Biographical-Item
Clinical Neurology
John R. Mantsch, Gavin Bart, Ellen M. Unterwald
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Elizabeth M. Doncheck, Eden M. Anderson, Chaz D. Konrath, Gage T. Liddiard, Margot C. DeBaker, Luke A. Urbanik, Matthew C. Hearing, John R. Mantsch
Summary: This study found that E2 activates ER beta and GPER1 in the PrL-PFC to attenuate the GABA-mediated constraint of key outputs that mediate cocaine seeking.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Microbiology
Abigail J. Perrin, Claudine Bisson, Peter A. Faull, Matthew J. Renshaw, Rebecca A. Lees, Roland A. Fleck, Helen R. Saibil, Ambrosius P. Snijders, David A. Baker, Michael J. Blackmanm
Summary: The protein SEA1 in Plasmodium falciparum plays a crucial role in the correct segregation of replicated DNA and formation of daughter merozoites during parasite development. Disruption of SEA1 expression results in defective merozoite development with some lacking nuclei, impacting egress. These findings suggest that SEA1 acts as an essential regulator in ensuring proper packaging of nuclei within merozoites, rather than directly facilitating egress.
Article
Public, Environmental & Occupational Health
Amir M. Forati, Rina Ghose, John R. Mantsch
Summary: Through geospatial analysis and multiscale geographically weighted regression, this study examined the determinants of opioid overdose deaths at the community level in Milwaukee County, identifying significant racialized health disparities. The findings showed that community-level factors play a crucial role in overdose risk, emphasizing the importance of targeted community-level solutions.
JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE
(2021)
Article
Public, Environmental & Occupational Health
Rina Ghose, Amir M. Forati, John R. Mantsch
Summary: The opioid crisis has had varying effects on urban communities with different socioeconomic backgrounds, leading to widening health disparities. The onset of the COVID-19 pandemic coincided with a significant increase in drug overdose deaths in the USA. This study used spatiotemporal analysis techniques to examine the impact of the COVID-19 pandemic on opioid overdose deaths and found that the pandemic significantly increased the monthly overdose deaths. The effects were particularly severe in poor, urban neighborhoods, affecting Black and Hispanic communities, but more affluent, suburban White communities also experienced an increase in overdose deaths.
JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE
(2022)
Article
Neurosciences
Kelsey C. Benton, Daniel S. Wheeler, Beliz Kurtoglu, Mahshid Bagher Zadeh Ansari, Daniel P. Cibich, Dante A. Gonzalez, Matthew R. Herbst, Saema Khursheed, Rachel C. Knorr, Doug Lobner, Jenree G. Maglasang, Kayla E. Rohr, Analisa Taylor, Robert C. Twining, Paul J. Witt, Paul J. Gasser
Summary: Norepinephrine has various effects on astrocytes, including metabolic, neuroprotective, and immunoregulatory functions. Recent studies have shown the presence of adrenergic receptors and catecholamine transporters on the plasma and nuclear membranes of astrocytes. The functionality of these receptors at the nuclear membrane has been demonstrated, suggesting a novel mechanism by which norepinephrine may directly influence nuclear processes.
Article
Microbiology
Avnish Patel, Stephanie D. Nofal, Michael J. Blackman, David A. Baker
Summary: This study investigates the role of CDC50 proteins in Plasmodium falciparum and shows that CDC50B binds to GC alpha, regulating egress efficiency, while CDC50C plays a critical role in trophozoite maturation.
Review
Biology
Paul W. Andrews, Catherine Bosyj, Luke Brenton, Laura Green, Paul J. Gasser, Christopher A. Lowry, Virginia M. Pickel
Summary: In the conventional model of serotonin neurotransmission, serotonin primarily acts on forebrain neurons through post-synaptic receptors and is taken back up by the serotonin reuptake transporter (SERT). However, accumulating evidence suggests that serotonin can also diffuse through cell membranes and enter forebrain neurons through multiple transporters. This alternative uptake method has been largely overlooked and has limited our understanding of serotonin's role in the brain.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Article
Microbiology
Lindsay B. Stewart, Aline Freville, Till S. Voss, David A. Baker, Gordon A. Awandare, David J. Conway
Summary: Asexual blood-stage malaria parasites must produce sexual progeny for mosquito infection. Two different methods of commitment rate measurement were compared, with higher sensitivity and precision observed in the detection of an early differentiation marker. Clinical isolates and laboratory-adapted lines showed significant variation in commitment rates, and the effects of choline on commitment varied quantitatively.
MICROBIOLOGY SPECTRUM
(2022)
Article
Substance Abuse
Amir Forati, Rina Ghose, Fahimeh Mohebbi, John R. Mantsch
Summary: This study applied geospatial analysis to examine the characteristics of the journey to drug overdose deaths in Milwaukee, Wisconsin. The research found that the community of residence is often different from the community where the overdose death occurs. Furthermore, the study identified different types of hotspots for overdose deaths and revealed insights into the drugs involved and causes of death.
DRUG AND ALCOHOL DEPENDENCE
(2023)
Article
Neurosciences
Jayme R. McReynolds, Colten P. Wolf, Dylan M. Starck, Jacob C. Mathy, Rebecca Schaps, Leslie A. Krause, Cecilia J. Hillard, John R. Mantsch
Summary: Stress promotes drug use in individuals with substance use disorders (SUDs). The CB1 cannabinoid receptor plays a crucial role in the stress-induced escalation of cocaine self-administration in male rats. The mesolimbic CB1 receptors are required for increased intake and heightened relapse susceptibility, suggesting that repeated stress at the time of cocaine use regulates CB1 receptor activity, though the exact mechanism is still unknown.
NEUROPSYCHOPHARMACOLOGY
(2023)