Article
Biochemistry & Molecular Biology
Idaira Oliva, Melissa M. Donate, Merridee J. Lefner, Matthew J. Wanat
Summary: Research shows that acute stress affects dopamine-dependent behaviors through activating CRF signaling in the ventral tegmental area (VTA), leading to suppression of motivation for food rewards but promotion of drug-seeking behavior. Additionally, prior drug experience may alter how CRF regulates motivation for food rewards in the VTA.
Article
Neurosciences
James R. Melchior, Rafael E. Perez, Gregory J. Salimando, Joseph R. Luchsinger, Aakash Basu, Danny G. Winder
Summary: This study reveals a dopamine-mediated cellular inhibition mechanism in the dBNST, suggesting that dopamine terminal autoreceptor activation and dopamine transporter blockade can affect the duration of catecholamine signals. Furthermore, cocaine enhances cellular inhibition in the dBNST in a drug reinforcement paradigm.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Chemistry, Medicinal
Nazzareno Cannella, Anna Maria Borruto, Michele Petrella, Maria Vittoria Micioni Di Bonaventura, Laura Soverchia, Carlo Cifani, Sara De Carlo, Esi Domi, Massimo Ubaldi
Summary: The neuropeptide S (NPS) and its receptor (NPSR) play an important role in the processing of emotional and affective behavior. NPS has both anxiolytic and arousal-promoting effects. It reduces alcohol consumption in alcohol-preferring rats and increases the anxiolytic effects in rodents with a history of alcohol dependence. These findings suggest that the NPS/NPSR system could be a potential target for treating alcohol and cocaine abuse.
Article
Pharmacology & Pharmacy
Fabrizio Sanna, Maria Antonietta De Luca
Summary: Oxytocin plays a role in regulating various centrally-mediated functions, including socio-sexual behavior, maternal care, affiliation, fear, stress, and anxiety. Research has shown that oxytocin modulates reward-related neural substrates, potentially offering therapeutic benefits for addiction, with the bed nucleus of the stria terminalis highlighted as a key structure in rebalancing altered neurochemical processes associated with dependence and relapse.
CURRENT OPINION IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Ana Domi, Veronica Lunerti, Michele Petrella, Esi Domi, Anna Maria Borruto, Massimo Ubaldi, Friedbert Weiss, Roberto Ciccocioppo
Summary: Genetic deletion or pharmacological blockade of NOP receptors have shown to reduce nicotine intake and motivation to self-administer in rats. The NOP receptor antagonist LY2817412 decreased nicotine intake in wild-type rats, confirming its effect is mediated by inhibition of NOP transmission. Injection of LY2817412 into the VTA decreased nicotine self-administration, suggesting that NOP receptor antagonism may be a potential treatment for smoking cessation.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Rachel Chudoba, Joanna Dabrowska
Summary: Defensive behaviors in response to threats are common across the animal kingdom. Different populations of CRF neurons in the CeA and BNST play divergent but complementary roles in mediating defensive responses, such as vigilance, avoidance, and active escape. Understanding the contributions of specific CRF neurons is important for understanding their dysregulation in fear and anxiety disorders.
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)
Article
Neurosciences
Catherine S. Thomas, Aida Mohammadkhani, Madiha Rana, Min Qiao, Corey Baimel, Stephanie L. Borgland
Summary: Reward and reinforcement processes are critical for survival and propagation of genes, with mesolimbic dopamine playing a central role. Optogenetic stimulation of orexin/dynorphin inputs in the VTA potentiates dopamine release in the NAc core, resulting in real time and conditioned place preference as well as increased food cue-directed orientation. While dynorphin contributes to aversive conditioning, the rewarding effects of LH orexin/dynorphin stimulation in the VTA are primarily driven by orexin rather than dynorphin.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Neurosciences
Marta E. Soden, Joshua X. Yee, Beatriz Cuevas, Ariana Rastani, Jordan Elum, Larry S. Zweifel
Summary: Neuropeptides play an important role in modulating mesolimbic system function. The bed nucleus of the stria terminalis (BNST) is identified as a major source of the neuropeptides neurotensin (NTS), corticotrophin releasing factor (CRF), and neurokinin B (NkB) in the ventral tegmental area (VTA). Analysis of calcium dynamics reveals both common and distinct activation patterns of these neuropeptide inputs during appetitive and aversive conditioning in the VTA.
FRONTIERS IN NEURAL CIRCUITS
(2022)
Article
Biochemistry & Molecular Biology
Yan Cheng, Rachael Elizabeth Dempsey, Soheil Kazemi Roodsari, Dorela D. Shuboni-Mulligan, Olivier George, Larry D. Sanford, Ming-Lei Guo
Summary: Cocaine can activate microglia and induce neuroinflammation in a region- and sex-specific manner. This study found that cocaine increased NLRP3 inflammasome activity and CRF levels in the striatum of males, while in females, it increased NLRP3 inflammasome activity in the hippocampus. NF-kappaB levels were increased by cocaine in both sexes. These findings highlight the importance of considering sex differences in neuroimmune signaling and developing sex-specific therapeutic approaches for cocaine use disorders.
Article
Biochemistry & Molecular Biology
Kasey S. Girven, Sonia Aroni, Jovana Navarrete, Rosa A. M. Marino, Paige N. McKeon, Joseph F. Cheer, Dennis R. Sparta
Summary: The insular cortex (IC) sends glutamatergic projections to vBNST-VTA neurons, activating IC-vBNST terminals may strengthen behavior in a dopamine-dependent manner, while silencing the IC-vBNST projection may lead to anxiety-like behavior, providing a potential mechanism for how the IC processes external triggers predictive of rewards.
Article
Neurosciences
Dominik Fiedler, Manju Sasi, Robert Blum, Christopher M. Klinke, Marta Andreatta, Hans-Christian Pape, Maren D. Lange
Summary: Researchers have identified that the oval nucleus of the bed nucleus of the stria terminalis (ovBNST) is rich in brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptor, which interact to reduce neuronal excitability and mediate long-term depression (LTD) in ovBNST neurons. This suggests that BDNF/TrkB signaling is a critical regulator of synaptic activity in ovBNST, dampening excitability at short and long time scales, and providing a potential entry point for adaptation to stressful environmental encounters, particularly in mediating maladaptive behaviors associated with stress exposure.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Marie A. Doyle, Jordan A. Brown, Danny G. Winder
Summary: This study found that the expression of GluN2D subunit is influenced during stress coping, which in turn affects coping strategies. The results suggest that GluN2D subunit plays a critical role in stress coping and may serve as a novel therapeutic target to consider for stress-related mood disorders.
Article
Neurosciences
A. Caffrey, E. Lavecchia, R. Merkel, Y. Zhang, K. S. Chichura, M. R. Hayes, R. P. Doyle, H. D. Schmidt
Summary: More effective treatments for fentanyl use disorder are urgently needed. Recently, a dual agonist of GLP-1Rs and Y2Rs was developed to attenuate fentanyl taking and seeking in rats without producing adverse effects. This study investigated the efficacy of Y2R agonism alone in reducing fentanyl self-administration and reinstatement of fentanyl-seeking in opioid-experienced rats.
Article
Neurosciences
Angela E. Snyder, Yuval Silberman
Summary: Alcohol Use Disorder and Substance Use Disorder impact millions of individuals in the United States, and stress is a key trigger for relapse in patients. The brain region BNST plays a crucial role in drug-seeking behaviors and stress responses.
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)
Article
Neurosciences
Mitchell G. Spring, Aaron Caccamise, Elizabeth A. Panther, Bethany M. Windsor, Karan R. Soni, Jayme R. McReynolds, Daniel S. Wheeler, John R. Mantsch, Robert A. Wheeler
Summary: Chronic stress diminishes task-related activity of brain pathways regulating approach behavior, reducing cue-directed behavior and impairing associated cortical activity. Stress disrupts reward processing by altering the incentive value of associated cues.
JOURNAL OF NEUROSCIENCE
(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)