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  1. Article ; Online: Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors.

    Hersey, Melinda / Bartole, Mattingly K / Jones, Claire S / Newman, Amy Hauck / Tanda, Gianluigi

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 13

    Abstract: Psychostimulant use disorders (PSUD) affect a growing number of men and women and exert sizable public health and economic burdens on our global society. Notably, there are some sex differences in the onset of dependence, relapse rates, and treatment ... ...

    Abstract Psychostimulant use disorders (PSUD) affect a growing number of men and women and exert sizable public health and economic burdens on our global society. Notably, there are some sex differences in the onset of dependence, relapse rates, and treatment success with PSUD observed in preclinical and clinical studies. The subtle sex differences observed in the behavioral aspects of PSUD may be associated with differences in the neurochemistry of the dopaminergic system between sexes. Preclinically, psychostimulants have been shown to increase synaptic dopamine (DA) levels and may downregulate the dopamine transporter (DAT). This effect is greatest in females during the high estradiol phase of the estrous cycle. Interestingly, women have been shown to be more likely to begin drug use at younger ages and report higher levels of desire to use cocaine than males. Even though there is currently no FDA-approved medication, modafinil, a DAT inhibitor approved for use in the treatment of narcolepsy and sleep disorders, has shown promise in the treatment of PSUD among specific populations of affected individuals. In this review, we highlight the therapeutic potential of modafinil and other atypical DAT inhibitors focusing on the lack of sex differences in the actions of these agents.
    MeSH term(s) Female ; Humans ; Male ; Dopamine Uptake Inhibitors/pharmacology ; Modafinil/therapeutic use ; Modafinil/pharmacology ; Sex Characteristics ; Benzhydryl Compounds/pharmacology ; Benzhydryl Compounds/therapeutic use ; Central Nervous System Stimulants/pharmacology ; Cocaine/pharmacology ; Dopamine
    Chemical Substances Dopamine Uptake Inhibitors ; Modafinil (R3UK8X3U3D) ; Benzhydryl Compounds ; Central Nervous System Stimulants ; Cocaine (I5Y540LHVR) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2023-07-07
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28135270
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: An FSCV Study on the Effects of Targeted Typical and Atypical DAT Inhibition on Dopamine Dynamics in the Nucleus Accumbens Shell of Male and Female Mice.

    Hersey, Melinda / Chen, Andy Y / Bartole, Mattingly K / Anand, Jayati / Newman, Amy Hauck / Tanda, Gianluigi

    ACS chemical neuroscience

    2023  Volume 14, Issue 15, Page(s) 2802–2810

    Abstract: Understanding the neurochemistry underlying sex differences in psychostimulant use disorders (PSUD) is essential for developing related therapeutics. Many psychostimulants, like cocaine, inhibit the dopamine transporter (DAT), which is largely thought to ...

    Abstract Understanding the neurochemistry underlying sex differences in psychostimulant use disorders (PSUD) is essential for developing related therapeutics. Many psychostimulants, like cocaine, inhibit the dopamine transporter (DAT), which is largely thought to account for actions related to their misuse and dependence. Cocaine-like, typical DAT inhibitors preferentially bind DAT in an outward-facing conformation, while atypical DAT inhibitors, like modafinil, prefer a more inward-facing DAT conformation. Modafinil and
    MeSH term(s) Female ; Mice ; Male ; Animals ; Modafinil/pharmacology ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Dopamine/metabolism ; Nucleus Accumbens/metabolism ; Mice, Inbred C57BL ; Central Nervous System Stimulants/pharmacology ; Cocaine/pharmacology ; Cocaine/metabolism ; Dopamine Uptake Inhibitors/pharmacology
    Chemical Substances JJC8-091 ; Modafinil (R3UK8X3U3D) ; JJC8-088 ; Dopamine Plasma Membrane Transport Proteins ; Dopamine (VTD58H1Z2X) ; Central Nervous System Stimulants ; Cocaine (I5Y540LHVR) ; Dopamine Uptake Inhibitors
    Language English
    Publishing date 2023-07-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ISSN 1948-7193
    ISSN (online) 1948-7193
    DOI 10.1021/acschemneuro.3c00354
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.

    Hersey, Melinda / Mereu, Maddalena / Jones, Claire S / Bartole, Mattingly K / Chen, Andy Y / Cao, Jianjing / Hiranita, Takato / Chun, Lauren E / Lopez, Jessica P / Katz, Jonathan L / Newman, Amy Hauck / Tanda, Gianluigi

    The European journal of neuroscience

    2024  

    Abstract: Psychostimulant use disorders (PSUD) are prevalent; however, no FDA-approved medications have been made available for treatment. Previous studies have shown that dual inhibitors of the dopamine transporter (DAT) and sigma receptors significantly reduce ... ...

    Abstract Psychostimulant use disorders (PSUD) are prevalent; however, no FDA-approved medications have been made available for treatment. Previous studies have shown that dual inhibitors of the dopamine transporter (DAT) and sigma receptors significantly reduce the behavioral/reinforcing effects of cocaine, which have been associated with stimulation of extracellular dopamine (DA) levels resulting from DAT inhibition. Here, we employ microdialysis and fast scan cyclic voltammetry (FSCV) procedures to investigate the effects of dual inhibitors of DAT and sigma receptors in combination with cocaine on nucleus accumbens shell (NAS) DA dynamics in naïve male Sprague Dawley rats. In microdialysis studies, administration of rimcazole (3, 10 mg/kg; i.p.) or its structural analog SH 3-24 (1, 3 mg/kg; i.p.), compounds that are dual inhibitors of DAT and sigma receptors, significantly reduced NAS DA efflux stimulated by increasing doses of cocaine (0.1, 0.3, 1.0 mg/kg; i.v.). Using the same experimental conditions, in FSCV tests, we show that rimcazole pretreatments attenuated cocaine-induced stimulation of evoked NAS DA release but produced no additional effect on DA clearance rate. Under the same conditions, JJC8-091, a modafinil analog and dual inhibitor of DAT and sigma receptors, similarly attenuated cocaine-induced stimulation of evoked NAS DA release but produced no additional effect on DA clearance rate. Our results provide the neurochemical groundwork towards understanding actions of dual inhibitors of DAT and sigma receptors on DA dynamics that likely mediate the behavioral effects of psychostimulants like cocaine.
    Language English
    Publishing date 2024-03-05
    Publishing country France
    Document type Journal Article
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.16293
    Database MEDical Literature Analysis and Retrieval System OnLINE

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