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  1. Article ; Online: Influence of social rank on the development of long-term ethanol drinking trajectories in cynomolgus monkeys.

    Galbo-Thomma, Lindsey K / Davenport, April T / Epperly, Phillip M / Czoty, Paul W

    Alcohol, clinical & experimental research

    2023  Volume 47, Issue 10, Page(s) 1943–1951

    Abstract: Background: Chronic stress contribute to the development of alcohol use disorder (AUD). However, characterizing the role of chronic social stressors in the development of problematic drinking trajectories in humans is complicated by practical and ... ...

    Abstract Background: Chronic stress contribute to the development of alcohol use disorder (AUD). However, characterizing the role of chronic social stressors in the development of problematic drinking trajectories in humans is complicated by practical and ethical constraints. Group-housed nonhuman primates develop social dominance hierarchies that represent a continuum of social experiences from enrichment in higher-ranked (dominant) monkeys to chronic social stress in lower-ranked (subordinate) individuals. This framework provides a translationally relevant model of chronic social stress that can be used to characterize its effects on vulnerability to AUD.
    Methods: Twelve male cynomolgus monkeys living in three social groups with established social dominance hierarchies were provided access to ethanol and water for 22 h/day, 4-5 days/week, for 1 year. Ethanol-free periods (2- or 3-day "weekends" or longer periods up to 10 days) were spent in social groups to maintain the stability of the social hierarchies. Observational studies conducted 6 months into the year of drinking assessed signs of ethanol withdrawal. After 1 year, monkeys were individually housed 24 h/day, 7 days/week for four consecutive weeks to examine the effect of eliminating the "weekends" spent socially housed.
    Results: Subordinate monkeys had significantly higher mean daily ethanol intakes than dominant monkeys across 1 year of open access. Subordinates also had higher intakes on the first day back drinking following ethanol-free periods of 9-10 days. Moreover, during the last 4 weeks of open access, intakes on the first drinking day after an ethanol-free weekend increased significantly in subordinate monkeys. This effect diminished when all monkeys were individually housed for 4 weeks, indicating that the increased intake in subordinates was driven by the social environment.
    Conclusions: These data demonstrate that social subordination, which is associated with chronic social stress, results in increased vulnerability to the development and maintenance of heavy drinking trajectories.
    Language English
    Publishing date 2023-08-27
    Publishing country United States
    Document type Journal Article
    ISSN 2993-7175
    ISSN (online) 2993-7175
    DOI 10.1111/acer.15163
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effect of chronic binge-like ethanol consumption on subsequent cocaine reinforcement in rhesus monkeys.

    Tryhus, Aaron M / Epperly, Phillip M / Davenport, April T / Galbo, Lindsey K / Czoty, Paul W

    Drug and alcohol dependence

    2021  Volume 223, Page(s) 108707

    Abstract: Background: Although most individuals with cocaine use disorder also abuse alcohol, little is known about the behavioral and pharmacological mechanisms that promote co-abuse. For example, it is unclear whether prior experience with alcohol renders ... ...

    Abstract Background: Although most individuals with cocaine use disorder also abuse alcohol, little is known about the behavioral and pharmacological mechanisms that promote co-abuse. For example, it is unclear whether prior experience with alcohol renders individuals more sensitive to cocaine when it is subsequently experienced.
    Methods: This study examined the effects of chronic ethanol consumption on subsequent cocaine reinforcement in rhesus monkeys. Six monkeys consumed 2.0 g/kg ethanol in a binge-drinking paradigm and 6 monkeys drank a non-alcoholic solution 5 days per week. After 9 months, each monkey's sensitivity to acquiring cocaine self-administration was determined. Monkeys performed an operant response resulting in food pellet delivery under a fixed-ratio 30 schedule of reinforcement. Saline, then ascending doses of cocaine, were substituted for food pellets until a cocaine dose was reached at which the number of cocaine injections delivered differed significantly from saline injections delivered. Following acquisition, a complete cocaine dose-effect curve was generated to determine whether ethanol consumption altered the reinforcing potency of cocaine determined by calculating the ED
    Results: Although individual variability was observed, the cocaine dose which initially served as a reinforcer did not differ between ethanol-drinking and control groups and, within the ethanol-drinking group, was not related to the amount of ethanol consumed. Moreover, the reinforcing potency of cocaine did not differ between groups.
    Conclusion: Taken together, the data suggest that a history of binge-like alcohol consumption does not affect sensitivity to cocaine when it is subsequently first experienced.
    MeSH term(s) Alcohol Drinking ; Animals ; Cocaine ; Conditioning, Operant ; Dose-Response Relationship, Drug ; Ethanol ; Macaca mulatta ; Reinforcement Schedule ; Self Administration
    Chemical Substances Ethanol (3K9958V90M) ; Cocaine (I5Y540LHVR)
    Language English
    Publishing date 2021-04-10
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 519918-9
    ISSN 1879-0046 ; 0376-8716
    ISSN (online) 1879-0046
    ISSN 0376-8716
    DOI 10.1016/j.drugalcdep.2021.108707
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  3. Article ; Online: Punishment of ethanol choice in rhesus monkeys.

    Stinson, Benjamin T / Galbo, Lindsey K / Flynn, Shawn M / Gouin, Angelique / Epperly, Phillip M / Davenport, April T / Czoty, Paul W

    Behavioural pharmacology

    2022  Volume 33, Issue 6, Page(s) 395–401

    Abstract: A defining characteristic of individuals diagnosed with alcohol use disorder (AUD) is that negative outcomes related to drinking do not lead them to reduce their alcohol use. In rodent models of AUD, this characteristic has been studied by adding the ... ...

    Abstract A defining characteristic of individuals diagnosed with alcohol use disorder (AUD) is that negative outcomes related to drinking do not lead them to reduce their alcohol use. In rodent models of AUD, this characteristic has been studied by adding the bitter tastant quinine to an ethanol solution. In this study, we extended this approach to a nonhuman primate model in which the ability of quinine to decrease the choice of a 4% ethanol solution vs. water was measured. Five adult female rhesus monkeys with 7.3 years of experience drinking ethanol were given access to a 4% ethanol solution and water for 3 h per day. When ethanol choice was stable, a single quinine concentration (0.03-5.6 g /L) was added to the ethanol solution for 1 day until a quinine concentration-effect curve was generated. After determining the quinine concentration that reduced ethanol choice by half (the quinine EC 50 ), the relative reinforcing strength of ethanol was manipulated by adding quinine or sucrose to the water alternative depending on the monkey's baseline choice. Adding quinine to ethanol produced a concentration-dependent decrease in ethanol choice and intake. Importantly, water intake increased, indicating an effect on response allocation rather than simply a decrease in fluid consumption. Consistent with this conclusion, the addition of quinine or sucrose to the water alternative resulted in predictable increases and decreases, respectively, in ethanol choice. These studies establish a model of punishment of ethanol choice in nonhuman primates that can be used to understand the contextual, biologic and pharmacologic factors that influence sensitivity to the punishment of alcohol drinking.
    MeSH term(s) Alcohol Drinking/drug therapy ; Alcoholism ; Animals ; Ethanol/pharmacology ; Female ; Macaca mulatta ; Punishment ; Quinine/pharmacology ; Sucrose ; Water
    Chemical Substances Water (059QF0KO0R) ; Ethanol (3K9958V90M) ; Sucrose (57-50-1) ; Quinine (A7V27PHC7A)
    Language English
    Publishing date 2022-08-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1027374-8
    ISSN 1473-5849 ; 0955-8810
    ISSN (online) 1473-5849
    ISSN 0955-8810
    DOI 10.1097/FBP.0000000000000683
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Preclinical Evaluation of Azabenzimidazole-Based PET Radioligands for γ-8 Dependent Transmembrane AMPA Receptor Regulatory Protein Imaging.

    Chen, Jiahui / Li, Yinlong / Yu, Qingzhen / Patel, Jimmy S / Zhou, Xin / Zhang, Kuo / Rong, Jian / Zhao, Chunyu / Chaudhary, Ahmad F / Zhang, Wei / Bi, Chunyang / Song, Zhendong / Davenport, April T / Daunais, James B / Haider, Ahmed / Collier, Lee / Yuan, Hongjie / Liang, Steven

    Chembiochem : a European journal of chemical biology

    2024  Volume 25, Issue 6, Page(s) e202300813

    Abstract: AMPA glutamate receptors (AMPARs) play a pivotal role in excitatory neurotransmission, particularly in the hippocampus where the TARP γ-8 subunit is enriched and serves as a target for emerging anti-epileptic drugs. To enable in vivo visualization of ... ...

    Abstract AMPA glutamate receptors (AMPARs) play a pivotal role in excitatory neurotransmission, particularly in the hippocampus where the TARP γ-8 subunit is enriched and serves as a target for emerging anti-epileptic drugs. To enable in vivo visualization of TARP γ-8 distribution and expression by positron emission tomography (PET), this study focuses on the development of novel
    MeSH term(s) Rats ; Animals ; Receptors, AMPA/metabolism ; Positron-Emission Tomography/methods ; Hippocampus
    Chemical Substances Receptors, AMPA
    Language English
    Publishing date 2024-02-19
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020469-3
    ISSN 1439-7633 ; 1439-4227
    ISSN (online) 1439-7633
    ISSN 1439-4227
    DOI 10.1002/cbic.202300813
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  5. Article: Rich Club Characteristics of Alcohol-Naïve Functional Brain Networks Predict Future Drinking Phenotypes in Rhesus Macaques.

    Rowland, Jared A / Stapleton-Kotloski, Jennifer R / Alberto, Greg E / Davenport, April T / Epperly, Phillip M / Godwin, Dwayne W / Daunais, James B

    Frontiers in behavioral neuroscience

    2021  Volume 15, Page(s) 673151

    Abstract: ... ...

    Abstract Purpose
    Language English
    Publishing date 2021-06-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452960-6
    ISSN 1662-5153
    ISSN 1662-5153
    DOI 10.3389/fnbeh.2021.673151
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  6. Article ; Online: Imaging Leucine-Rich Repeat Kinase 2 In Vivo with

    Chen, Zhen / Chen, Jiahui / Chen, Laigao / Yoo, Chi-Hyeon / Rong, Jian / Fu, Hualong / Shao, Tuo / Coffman, Karen / Steyn, Stefanus J / Davenport, April T / Daunais, James B / Haider, Ahmed / Collier, Lee / Josephson, Lee / Wey, Hsiao-Ying / Zhang, Lei / Liang, Steven H

    Journal of medicinal chemistry

    2022  Volume 66, Issue 3, Page(s) 1712–1724

    Abstract: Leucine-rich repeat kinase 2 (LRRK2) has been demonstrated to be closely involved in the pathogenesis of Parkinson's disease (PD), and pharmacological blockade of LRRK2 represents a new opportunity for therapeutical treatment of PD and other related ... ...

    Abstract Leucine-rich repeat kinase 2 (LRRK2) has been demonstrated to be closely involved in the pathogenesis of Parkinson's disease (PD), and pharmacological blockade of LRRK2 represents a new opportunity for therapeutical treatment of PD and other related neurodegenerative conditions. The development of an LRRK2-specific positron emission tomography (PET) ligand would enable a target occupancy study in vivo and greatly facilitate LRRK2 drug discovery and clinical translation as well as provide a molecular imaging tool for studying physiopathological changes in neurodegenerative diseases. In this work, we present the design and development of compound
    MeSH term(s) Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Leucine/metabolism ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism ; Ligands ; Parkinson Disease/metabolism ; Positron-Emission Tomography/methods
    Chemical Substances Leucine (GMW67QNF9C) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (EC 2.7.11.1) ; Ligands ; (18F)PF-06455943
    Language English
    Publishing date 2022-10-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.2c00551
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  7. Article ; Online: Effects of alcohol on c-Myc protein in the brain.

    Akinyeke, Tunde / Weber, Sydney J / Davenport, April T / Baker, Erich J / Daunais, James B / Raber, Jacob

    Behavioural brain research

    2017  Volume 320, Page(s) 356–364

    Abstract: Alcoholism is a disorder categorized by significant impairment that is directly related to persistent and extreme use of alcohol. The effects of alcoholism on c-Myc protein expression in the brain have been scarcely studied. This is the first study to ... ...

    Abstract Alcoholism is a disorder categorized by significant impairment that is directly related to persistent and extreme use of alcohol. The effects of alcoholism on c-Myc protein expression in the brain have been scarcely studied. This is the first study to investigate the role different characteristics of alcoholism have on c-Myc protein in the brain. We analyzed c-Myc protein in the hypothalamus and amygdala from five different animal models of alcohol abuse. c-Myc protein was increased following acute ethanol exposure in a mouse knockout model and following chronic ethanol consumption in vervet monkeys. We also observed increases in c-Myc protein exposure in animals that are genetically predisposed to alcohol and methamphetamine abuse. Lastly, c-Myc protein was increased in animals that were acutely exposed to methamphetamine when compared to control treated animals. These results suggest that in substance abuse c-Myc plays an important role in the brain's response.
    Language English
    Publishing date 2017-03-01
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2016.11.009
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  8. Article: Synthesis and Biological Evaluation of Enantiomerically Pure (

    Korff, Marvin / Chaudhary, Ahmad / Li, Yinlong / Zhou, Xin / Zhao, Chunyu / Rong, Jian / Chen, Jiahui / Xiao, Zhiwei / Elghazawy, Nehal H / Sippl, Wolfgang / Davenport, April T / Daunais, James B / Wang, Lu / Abate, Carmen / Ahmed, Hazem / Crowe, Ron / Liang, Steven H / Ametamey, Simon M / Wünsch, Bernhard /
    Haider, Ahmed

    Research square

    2023  

    Abstract: GluN2B subunit- ... ...

    Abstract GluN2B subunit-containing
    Language English
    Publishing date 2023-01-27
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-2516002/v1
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  9. Article ; Online: Evaluation of [

    Haider, Ahmed / Wang, Lu / Gobbi, Luca / Li, Yinlong / Chaudhary, Ahmad / Zhou, Xin / Chen, Jiahui / Zhao, Chunyu / Rong, Jian / Xiao, Zhiwei / Hou, Lu / Elghazawy, Nehal H / Sippl, Wolfgang / Davenport, April T / Daunais, James B / Ahmed, Hazem / Crowe, Ron / Honer, Michael / Rominger, Axel /
    Grether, Uwe / Liang, Steven H / Ametamey, Simon M

    ACS chemical neuroscience

    2023  Volume 14, Issue 20, Page(s) 3752–3760

    Abstract: The cannabinoid type 2 receptor (CB2) has been implicated in a variety of central and peripheral inflammatory diseases, prompting significant interest in the development of CB2-targeted diagnostic and therapeutic agents. A validated positron emission ... ...

    Abstract The cannabinoid type 2 receptor (CB2) has been implicated in a variety of central and peripheral inflammatory diseases, prompting significant interest in the development of CB2-targeted diagnostic and therapeutic agents. A validated positron emission tomography (PET) radioligand for imaging CB2 in the living human brain as well as in peripheral tissues is currently lacking. As part of our research program, we have recently identified the trisubstituted pyridine, [
    MeSH term(s) Animals ; Humans ; Radiopharmaceuticals/metabolism ; Positron-Emission Tomography/methods ; Ligands ; Brain/diagnostic imaging ; Brain/metabolism ; Primates/metabolism ; Receptor, Cannabinoid, CB2/metabolism ; Fluorine Radioisotopes/metabolism ; Mammals/metabolism
    Chemical Substances Radiopharmaceuticals ; Ligands ; Receptor, Cannabinoid, CB2 ; Fluorine Radioisotopes
    Language English
    Publishing date 2023-10-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1948-7193
    ISSN (online) 1948-7193
    DOI 10.1021/acschemneuro.3c00222
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  10. Article ; Online: Synthesis and Biological Evaluation of Enantiomerically Pure (

    Korff, Marvin / Chaudhary, Ahmad / Li, Yinlong / Zhou, Xin / Zhao, Chunyu / Rong, Jian / Chen, Jiahui / Xiao, Zhiwei / Elghazawy, Nehal H / Sippl, Wolfgang / Davenport, April T / Daunais, James B / Wang, Lu / Abate, Carmen / Ahmed, Hazem / Crowe, Ron / Schmidt, Thomas J / Liang, Steven H / Ametamey, Simon M /
    Wünsch, Bernhard / Haider, Ahmed

    Journal of medicinal chemistry

    2023  Volume 66, Issue 23, Page(s) 16018–16031

    Abstract: GluN2B subunit- ... ...

    Abstract GluN2B subunit-containing
    MeSH term(s) Animals ; Humans ; Receptors, N-Methyl-D-Aspartate/metabolism ; Positron-Emission Tomography/methods ; Brain/diagnostic imaging ; Brain/metabolism ; Fluorine Radioisotopes
    Chemical Substances Fluorine-18 (GZ5I74KB8G) ; Receptors, N-Methyl-D-Aspartate ; Fluorine Radioisotopes
    Language English
    Publishing date 2023-11-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c01441
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