Behavioral and dopamine transporter binding properties of the modafinil analog (S, S)-CE-158: reversal of the motivational effects of tetrabenazine and enhancement of progressive ratio responding.
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| Title: | Behavioral and dopamine transporter binding properties of the modafinil analog (S, S)-CE-158: reversal of the motivational effects of tetrabenazine and enhancement of progressive ratio responding. |
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| Authors: | Rotolo, Renee A. (AUTHOR), Kalaba, Predrag (AUTHOR), Dragacevic, Vladimir (AUTHOR), Presby, Rose E. (AUTHOR), Neri, Julia (AUTHOR), Robertson, Emily (AUTHOR), Yang, Jen-Hau (AUTHOR), Correa, Merce (AUTHOR), Bakulev, Vasiliy (AUTHOR), Volkova, Natalia N. (AUTHOR), Pifl, Christian (AUTHOR), Lubec, Gert (AUTHOR), Salamone, John D. (AUTHOR) |
| Source: | Psychopharmacology. Nov2020, Vol. 237 Issue 11, p3459-3470. 12p. 1 Color Photograph, 1 Diagram, 4 Graphs. |
| Subjects: | Monoamine transporters, Nucleus accumbens, Mental depression, Symptoms, Dopamine, Entertainers |
| Abstract: | Rationale: Atypical dopamine (DA) transport blockers such as modafinil and its analogs may be useful for treating motivational symptoms of depression and other disorders. Previous research has shown that the DA depleting agent tetrabenazine can reliably induce motivational deficits in rats, as evidenced by a shift towards a low-effort bias in effort-based choice tasks. This is consistent with human studies showing that people with major depression show a bias towards low-effort activities. Objectives: Recent studies demonstrated that the atypical DA transport (DAT) inhibitor (S)-CE-123 reversed tetrabenazine-induced motivational deficits, increased progressive ratio (PROG) lever pressing, and increased extracellular DA in the nucleus accumbens. In the present studies, a recently synthesized modafinil analog, (S, S)-CE-158, was assessed in a series of neurochemical and behavioral studies in rats. Results: (S, S)-CE-158 demonstrated the ability to reverse the effort-related effects of tetrabenazine and increase selection of high-effort PROG lever pressing in rats tested on PROG/chow feeding choice task. (S, S)-CE-158 showed a high selectivity for inhibiting DAT compared with other monoamine transporters, and systemic administration of (S, S)-CE-158 increased extracellular DA in the nucleus accumbens during the behaviorally active time course, which is consistent with the effects of (S)-CE-123 and other DAT inhibitors that enhance high-effort responding. Conclusions: These studies provide an initial neurochemical characterization of a novel atypical DAT inhibitor, and demonstrate that this compound is active in models of effort-related choice. This research could contribute to the development of novel compounds for the treatment of motivational dysfunctions in humans. [ABSTRACT FROM AUTHOR] |
| Copyright of Psychopharmacology is the property of Springer Nature 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 |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 146477657 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Behavioral and dopamine transporter binding properties of the modafinil analog (S, S)-CE-158: reversal of the motivational effects of tetrabenazine and enhancement of progressive ratio responding. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Rotolo%2C+Renee+A%2E%22">Rotolo, Renee A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kalaba%2C+Predrag%22">Kalaba, Predrag</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dragacevic%2C+Vladimir%22">Dragacevic, Vladimir</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Presby%2C+Rose+E%2E%22">Presby, Rose E.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Neri%2C+Julia%22">Neri, Julia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Robertson%2C+Emily%22">Robertson, Emily</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yang%2C+Jen-Hau%22">Yang, Jen-Hau</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Correa%2C+Merce%22">Correa, Merce</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bakulev%2C+Vasiliy%22">Bakulev, Vasiliy</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Volkova%2C+Natalia+N%2E%22">Volkova, Natalia N.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pifl%2C+Christian%22">Pifl, Christian</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lubec%2C+Gert%22">Lubec, Gert</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Salamone%2C+John+D%2E%22">Salamone, John D.</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Nov2020, Vol. 237 Issue 11, p3459-3470. 12p. 1 Color Photograph, 1 Diagram, 4 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Monoamine+transporters%22">Monoamine transporters</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleus+accumbens%22">Nucleus accumbens</searchLink><br /><searchLink fieldCode="DE" term="%22Mental+depression%22">Mental depression</searchLink><br /><searchLink fieldCode="DE" term="%22Symptoms%22">Symptoms</searchLink><br /><searchLink fieldCode="DE" term="%22Dopamine%22">Dopamine</searchLink><br /><searchLink fieldCode="DE" term="%22Entertainers%22">Entertainers</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Rationale: Atypical dopamine (DA) transport blockers such as modafinil and its analogs may be useful for treating motivational symptoms of depression and other disorders. Previous research has shown that the DA depleting agent tetrabenazine can reliably induce motivational deficits in rats, as evidenced by a shift towards a low-effort bias in effort-based choice tasks. This is consistent with human studies showing that people with major depression show a bias towards low-effort activities. Objectives: Recent studies demonstrated that the atypical DA transport (DAT) inhibitor (S)-CE-123 reversed tetrabenazine-induced motivational deficits, increased progressive ratio (PROG) lever pressing, and increased extracellular DA in the nucleus accumbens. In the present studies, a recently synthesized modafinil analog, (S, S)-CE-158, was assessed in a series of neurochemical and behavioral studies in rats. Results: (S, S)-CE-158 demonstrated the ability to reverse the effort-related effects of tetrabenazine and increase selection of high-effort PROG lever pressing in rats tested on PROG/chow feeding choice task. (S, S)-CE-158 showed a high selectivity for inhibiting DAT compared with other monoamine transporters, and systemic administration of (S, S)-CE-158 increased extracellular DA in the nucleus accumbens during the behaviorally active time course, which is consistent with the effects of (S)-CE-123 and other DAT inhibitors that enhance high-effort responding. Conclusions: These studies provide an initial neurochemical characterization of a novel atypical DAT inhibitor, and demonstrate that this compound is active in models of effort-related choice. This research could contribute to the development of novel compounds for the treatment of motivational dysfunctions in humans. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Psychopharmacology is the property of Springer Nature 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: BibEntity: Identifiers: – Type: doi Value: 10.1007/s00213-020-05625-6 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 3459 Subjects: – SubjectFull: Monoamine transporters Type: general – SubjectFull: Nucleus accumbens Type: general – SubjectFull: Mental depression Type: general – SubjectFull: Symptoms Type: general – SubjectFull: Dopamine Type: general – SubjectFull: Entertainers Type: general Titles: – TitleFull: Behavioral and dopamine transporter binding properties of the modafinil analog (S, S)-CE-158: reversal of the motivational effects of tetrabenazine and enhancement of progressive ratio responding. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Rotolo, Renee A. – PersonEntity: Name: NameFull: Kalaba, Predrag – PersonEntity: Name: NameFull: Dragacevic, Vladimir – PersonEntity: Name: NameFull: Presby, Rose E. – PersonEntity: Name: NameFull: Neri, Julia – PersonEntity: Name: NameFull: Robertson, Emily – PersonEntity: Name: NameFull: Yang, Jen-Hau – PersonEntity: Name: NameFull: Correa, Merce – PersonEntity: Name: NameFull: Bakulev, Vasiliy – PersonEntity: Name: NameFull: Volkova, Natalia N. – PersonEntity: Name: NameFull: Pifl, Christian – PersonEntity: Name: NameFull: Lubec, Gert – PersonEntity: Name: NameFull: Salamone, John D. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 11 Text: Nov2020 Type: published Y: 2020 Identifiers: – Type: issn-print Value: 00333158 Numbering: – Type: volume Value: 237 – Type: issue Value: 11 Titles: – TitleFull: Psychopharmacology Type: main |
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