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Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.

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Title: Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.
Authors: Hersey, Melinda (AUTHOR), Mereu, Maddalena (AUTHOR), Jones, Claire S. (AUTHOR), Bartole, Mattingly K. (AUTHOR), Chen, Andy Y. (AUTHOR), Cao, Jianjing (AUTHOR), Hiranita, Takato (AUTHOR), Chun, Lauren E. (AUTHOR), Lopez, Jessica P. (AUTHOR), Katz, Jonathan L. (AUTHOR), Newman, Amy Hauck (AUTHOR), Tanda, Gianluigi (AUTHOR)
Source: European Journal of Neuroscience. May2024, Vol. 59 Issue 10, p2436-2449. 14p.
Subjects: Dopamine receptors, United States. Food & Drug Administration, Sigma receptors, Cocaine, Nucleus accumbens, Sprague Dawley rats, Dopamine, Rats, Cyclic voltammetry
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. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Label: Title
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  Data: Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.
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  Label: Authors
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  Data: <searchLink fieldCode="AR" term="%22Hersey%2C+Melinda%22">Hersey, Melinda</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mereu%2C+Maddalena%22">Mereu, Maddalena</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jones%2C+Claire+S%2E%22">Jones, Claire S.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bartole%2C+Mattingly+K%2E%22">Bartole, Mattingly K.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Andy+Y%2E%22">Chen, Andy Y.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cao%2C+Jianjing%22">Cao, Jianjing</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hiranita%2C+Takato%22">Hiranita, Takato</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chun%2C+Lauren+E%2E%22">Chun, Lauren E.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lopez%2C+Jessica+P%2E%22">Lopez, Jessica P.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Katz%2C+Jonathan+L%2E%22">Katz, Jonathan L.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Newman%2C+Amy+Hauck%22">Newman, Amy Hauck</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tanda%2C+Gianluigi%22">Tanda, Gianluigi</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. May2024, Vol. 59 Issue 10, p2436-2449. 14p.
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  Data: <searchLink fieldCode="DE" term="%22Dopamine+receptors%22">Dopamine receptors</searchLink><br /><searchLink fieldCode="DE" term="%22United+States%2E+Food+%26+Drug+Administration%22">United States. Food & Drug Administration</searchLink><br /><searchLink fieldCode="DE" term="%22Sigma+receptors%22">Sigma receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Cocaine%22">Cocaine</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleus+accumbens%22">Nucleus accumbens</searchLink><br /><searchLink fieldCode="DE" term="%22Sprague+Dawley+rats%22">Sprague Dawley rats</searchLink><br /><searchLink fieldCode="DE" term="%22Dopamine%22">Dopamine</searchLink><br /><searchLink fieldCode="DE" term="%22Rats%22">Rats</searchLink><br /><searchLink fieldCode="DE" term="%22Cyclic+voltammetry%22">Cyclic voltammetry</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: 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. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1111/ejn.16293
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 14
        StartPage: 2436
    Subjects:
      – SubjectFull: Dopamine receptors
        Type: general
      – SubjectFull: United States. Food & Drug Administration
        Type: general
      – SubjectFull: Sigma receptors
        Type: general
      – SubjectFull: Cocaine
        Type: general
      – SubjectFull: Nucleus accumbens
        Type: general
      – SubjectFull: Sprague Dawley rats
        Type: general
      – SubjectFull: Dopamine
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      – SubjectFull: Rats
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      – SubjectFull: Cyclic voltammetry
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      – TitleFull: Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.
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              Text: May2024
              Type: published
              Y: 2024
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