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  1. Article ; Online: Series of (([1,1'-Biphenyl]-2-yl)methyl)sulfinylalkyl Alicyclic Amines as Novel and High Affinity Atypical Dopamine Transporter Inhibitors with Reduced hERG Activity.

    Ku, Therese C / Cao, Jianjing / Won, Sung Joon / Guo, Jiqing / Camacho-Hernandez, Gisela A / Okorom, Amarachi V / Salomon, Kristine Walloe / Lee, Kuo Hao / Loland, Claus J / Duff, Henry J / Shi, Lei / Newman, Amy Hauck

    ACS pharmacology & translational science

    2024  Volume 7, Issue 2, Page(s) 515–532

    Abstract: Currently, there are no FDA-approved medications for the treatment of psychostimulant use disorders (PSUD). We have previously discovered "atypical" dopamine transporter (DAT) inhibitors that do not display psychostimulant-like behaviors and may be ... ...

    Abstract Currently, there are no FDA-approved medications for the treatment of psychostimulant use disorders (PSUD). We have previously discovered "atypical" dopamine transporter (DAT) inhibitors that do not display psychostimulant-like behaviors and may be useful as medications to treat PSUD. Lead candidates (e.g., JJC8-091,
    Language English
    Publishing date 2024-01-05
    Publishing country United States
    Document type Journal Article
    ISSN 2575-9108
    ISSN (online) 2575-9108
    DOI 10.1021/acsptsci.3c00322
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Synaptic-like axo-axonal transmission from striatal cholinergic interneurons onto dopaminergic fibers.

    Kramer, Paul F / Brill-Weil, Samuel G / Cummins, Alex C / Zhang, Renshu / Camacho-Hernandez, Gisela A / Newman, Amy H / Eldridge, Mark A G / Averbeck, Bruno B / Khaliq, Zayd M

    Neuron

    2022  Volume 110, Issue 18, Page(s) 2949–2960.e4

    Abstract: Transmission from striatal cholinergic interneurons (CINs) controls dopamine release through nicotinic acetylcholine receptors (nAChRs) on dopaminergic axons. Anatomical studies suggest that cholinergic terminals signal predominantly through non-synaptic ...

    Abstract Transmission from striatal cholinergic interneurons (CINs) controls dopamine release through nicotinic acetylcholine receptors (nAChRs) on dopaminergic axons. Anatomical studies suggest that cholinergic terminals signal predominantly through non-synaptic volume transmission. However, the influence of cholinergic transmission on electrical signaling in axons remains unclear. We examined axo-axonal transmission from CINs onto dopaminergic axons using perforated-patch recordings, which revealed rapid spontaneous EPSPs with properties characteristic of fast synapses. Pharmacology showed that axonal EPSPs (axEPSPs) were mediated primarily by high-affinity α6-containing receptors. Remarkably, axEPSPs triggered spontaneous action potentials, suggesting that these axons perform integration to convert synaptic input into spiking, a function associated with somatodendritic compartments. We investigated the cross-species validity of cholinergic axo-axonal transmission by recording dopaminergic axons in macaque putamen and found similar axEPSPs. Thus, we reveal that synaptic-like neurotransmission underlies cholinergic signaling onto dopaminergic axons, supporting the idea that striatal dopamine release can occur independently of somatic firing to provide distinct signaling.
    MeSH term(s) Axons/metabolism ; Cholinergic Agents ; Cholinergic Fibers/metabolism ; Corpus Striatum/physiology ; Dopamine/physiology ; Interneurons/metabolism ; Receptors, Nicotinic/metabolism ; Synaptic Transmission/physiology
    Chemical Substances Cholinergic Agents ; Receptors, Nicotinic ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2022-08-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2022.07.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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