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  1. Article ; Online: Lateral hypothalamic GABAergic neurons encode alcohol memories.

    Alonso-Lozares, Isis / Wilbers, Pelle / Asperl, Lina / Teijsse, Sem / van der Neut, Charlotte / Schetters, Dustin / van Mourik, Yvar / McDonald, Allison J / Heistek, Tim / Mansvelder, Huibert D / De Vries, Taco J / Marchant, Nathan J

    Current biology : CB

    2024  Volume 34, Issue 5, Page(s) 1086–1097.e6

    Abstract: In alcohol use disorder, the alcohol memories persist during abstinence, and exposure to stimuli associated with alcohol use can lead to relapse. This highlights the importance of investigating the neural substrates underlying not only relapse but also ... ...

    Abstract In alcohol use disorder, the alcohol memories persist during abstinence, and exposure to stimuli associated with alcohol use can lead to relapse. This highlights the importance of investigating the neural substrates underlying not only relapse but also encoding and expression of alcohol memories. GABAergic neurons in the lateral hypothalamus (LH-GABA) have been shown to be critical for food-cue memories and motivation; however, the extent to which this role extends to alcohol-cue memories and motivations remains unexplored. In this study, we aimed to describe how alcohol-related memories are encoded and expressed in LH GABAergic neurons. Our first step was to monitor LH-GABA calcium transients during acquisition, extinction, and reinstatement of an alcohol-cue memory using fiber photometry. We trained the rats on a Pavlovian conditioning task, where one conditioned stimulus (CS+) predicted alcohol (20% EtOH) and another conditioned stimulus (CS-) had no outcome. We then extinguished this association through non-reinforced presentations of the CS+ and CS- and finally, in two different groups, we measured relapse under non-primed and alcohol-primed induced reinstatement. Our results show that initially both cues caused increased LH-GABA activity, and after learning only the alcohol cue increased LH-GABA activity. After extinction, this activity decreases, and we found no differences in LH-GABA activity during reinstatement in either group. Next, we inhibited LH-GABA neurons with optogenetics to show that activity of these neurons is necessary for the formation of an alcohol-cue association. These findings suggest that LH-GABA might be involved in attentional processes modulated by learning.
    MeSH term(s) Rats ; Animals ; Hypothalamic Area, Lateral/physiology ; Learning ; Ethanol ; GABAergic Neurons ; Cues ; Recurrence ; gamma-Aminobutyric Acid
    Chemical Substances Ethanol (3K9958V90M) ; gamma-Aminobutyric Acid (56-12-2)
    Language English
    Publishing date 2024-02-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2024.01.076
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Alcohol Seeking Under Risk of Punishment Is Associated With Activation of Cortical and Subcortical Brain Regions.

    McDonald, Allison J / Alonso-Lozares, Isis / Rauh, Vasco / van Mourik, Yvar / Schetters, Dustin / De Vries, Taco J / Marchant, Nathan J

    Frontiers in behavioral neuroscience

    2021  Volume 15, Page(s) 739681

    Abstract: In humans, stimuli associated with alcohol availability can provoke relapse during abstinence. In this study, we investigated the role of discriminative stimuli (DS) in the control of alcohol seeking in two types of behavioral tests. The first test ... ...

    Abstract In humans, stimuli associated with alcohol availability can provoke relapse during abstinence. In this study, we investigated the role of discriminative stimuli (DS) in the control of alcohol seeking in two types of behavioral tests. The first test examined the ability of an alcohol-associated DS to promote alcohol seeking (relapse) after punishment-imposed abstinence in the presence of a different DS. Following this, we tested whether the differentially associated DS can promote and suppress alcohol self-administration in a within-session discrimination task. During the within-session discrimination task, we also tested the rate of alcohol self-administration when two DS are presented in a compound. We first trained Long-Evans male rats (
    Language English
    Publishing date 2021-10-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452960-6
    ISSN 1662-5153
    ISSN 1662-5153
    DOI 10.3389/fnbeh.2021.739681
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Role of anterior insula cortex in context-induced relapse of nicotine-seeking.

    Ghareh, Hussein / Alonso-Lozares, Isis / Schetters, Dustin / Herman, Rae J / Heistek, Tim S / Van Mourik, Yvar / Jean-Richard-Dit-Bressel, Philip / Zernig, Gerald / Mansvelder, Huibert D / De Vries, Taco J / Marchant, Nathan J

    eLife

    2022  Volume 11

    Abstract: Tobacco use is the leading cause of preventable death worldwide, and relapse during abstinence remains the critical barrier to successful treatment of tobacco addiction. During abstinence, environmental contexts associated with nicotine use can induce ... ...

    Abstract Tobacco use is the leading cause of preventable death worldwide, and relapse during abstinence remains the critical barrier to successful treatment of tobacco addiction. During abstinence, environmental contexts associated with nicotine use can induce craving and contribute to relapse. The insular cortex (IC) is thought to be a critical substrate of nicotine addiction and relapse. However, its specific role in context-induced relapse of nicotine-seeking is not fully known. In this study, we report a novel rodent model of context-induced relapse to nicotine-seeking after punishment-imposed abstinence, which models self-imposed abstinence through increasing negative consequences of excessive drug use. Using the neuronal activity marker Fos we find that the anterior (aIC), but not the middle or posterior IC, shows increased activity during context-induced relapse. Combining Fos with retrograde labeling of aIC inputs, we show projections to aIC from contralateral aIC and basolateral amygdala exhibit increased activity during context-induced relapse. Next, we used fiber photometry in aIC and observed phasic increases in aIC activity around nicotine-seeking responses during self-administration, punishment, and the context-induced relapse tests. Next, we used chemogenetic inhibition in both male and female rats to determine whether activity in aIC is necessary for context-induced relapse. We found that chemogenetic inhibition of aIC decreased context-induced nicotine-seeking after either punishment- or extinction-imposed abstinence. These findings highlight the critical role nicotine-associated contexts play in promoting relapse, and they show that aIC activity is critical for this context-induced relapse following both punishment and extinction-imposed abstinence.
    MeSH term(s) Animals ; Extinction, Psychological/physiology ; Female ; Male ; Nicotine/adverse effects ; Punishment ; Rats ; Recurrence ; Self Administration
    Chemical Substances Nicotine (6M3C89ZY6R)
    Language English
    Publishing date 2022-05-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.75609
    Database MEDical Literature Analysis and Retrieval System OnLINE

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