A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats
Reduced cognitive abilities are often characterized by an impairment of flexibility, i.e., the ability to switch from learned rules or categories that were important in certain contexts to different new modalities that rule the task. Drugs targeting the dopamine transporter (DAT) are widely used for...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Behavioral Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00222/full |
| _version_ | 1818063508109000704 |
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| author | Agnieszka Nikiforuk Predrag Kalaba Marija Ilic Volker Korz Vladimir Dragačević Judith Wackerlig Thierry Langer Harald Höger Joanna Golebiowska Piotr Popik Gert Lubec |
| author_facet | Agnieszka Nikiforuk Predrag Kalaba Marija Ilic Volker Korz Vladimir Dragačević Judith Wackerlig Thierry Langer Harald Höger Joanna Golebiowska Piotr Popik Gert Lubec |
| author_sort | Agnieszka Nikiforuk |
| collection | DOAJ |
| description | Reduced cognitive abilities are often characterized by an impairment of flexibility, i.e., the ability to switch from learned rules or categories that were important in certain contexts to different new modalities that rule the task. Drugs targeting the dopamine transporter (DAT) are widely used for their potential to enhance cognitive abilities. However, commercially available drugs are of limited specificity for DAT, blocking also noradrenaline and serotonine transporters, that can lead to unwanted side effects in healthy subjects. Therefore, we tested a newly synthetized compound (CE-123) with higher specificity for DAT in male rats in an attentional set-shifting task (ASST), that proves for cognitive flexibility and a 5-choice serial-reaction time task (5-CSRTT) assessing visuospatial attention and impulsivity. Treated rats at a dose of 0.3 and 1.0 but not 0.1 mg/kg bodyweight showed reduced extra-dimensional shifts in the ASST compared to controls indicating increased cognitive flexibility. Rats treated with R-Modafinil, a commercially available DAT inhibitor at a dose of 10 mg/kg bodyweight showed increased premature responses, an indicator of increased impulsivity, during a 10 s but not a 2.5, 5, or 7.5 s intertrial interval when compared to vehicle-treated rats in the 5-CSRTT. This was not found in rats treated with CE-123 at the same dose as for R-Modafinil. Visuospatial attention, except premature responses, did not differ between R-Modafinil and CE-123-treated rats and their respective controls. Thus, CE-123 increased cognitive flexibility with diminished impulsivity. |
| first_indexed | 2024-12-10T14:21:13Z |
| format | Article |
| id | doaj.art-8a6fb1a9aa7041c1b1baf84bc3560418 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-12-10T14:21:13Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-8a6fb1a9aa7041c1b1baf84bc35604182022-12-22T01:45:11ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532017-11-011110.3389/fnbeh.2017.00222300650A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male RatsAgnieszka Nikiforuk0Predrag Kalaba1Marija Ilic2Volker Korz3Vladimir Dragačević4Judith Wackerlig5Thierry Langer6Harald Höger7Joanna Golebiowska8Piotr Popik9Gert Lubec10Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, PolandDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaCenter for Brain Research, Medical University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaCore Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Vienna, AustriaDepartment of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, PolandDepartment of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, PolandParacelsus Medical University, Salzburg, AustriaReduced cognitive abilities are often characterized by an impairment of flexibility, i.e., the ability to switch from learned rules or categories that were important in certain contexts to different new modalities that rule the task. Drugs targeting the dopamine transporter (DAT) are widely used for their potential to enhance cognitive abilities. However, commercially available drugs are of limited specificity for DAT, blocking also noradrenaline and serotonine transporters, that can lead to unwanted side effects in healthy subjects. Therefore, we tested a newly synthetized compound (CE-123) with higher specificity for DAT in male rats in an attentional set-shifting task (ASST), that proves for cognitive flexibility and a 5-choice serial-reaction time task (5-CSRTT) assessing visuospatial attention and impulsivity. Treated rats at a dose of 0.3 and 1.0 but not 0.1 mg/kg bodyweight showed reduced extra-dimensional shifts in the ASST compared to controls indicating increased cognitive flexibility. Rats treated with R-Modafinil, a commercially available DAT inhibitor at a dose of 10 mg/kg bodyweight showed increased premature responses, an indicator of increased impulsivity, during a 10 s but not a 2.5, 5, or 7.5 s intertrial interval when compared to vehicle-treated rats in the 5-CSRTT. This was not found in rats treated with CE-123 at the same dose as for R-Modafinil. Visuospatial attention, except premature responses, did not differ between R-Modafinil and CE-123-treated rats and their respective controls. Thus, CE-123 increased cognitive flexibility with diminished impulsivity.http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00222/fullcognitive flexibilitynovel DAT inhibitorscognitive enhancementdiminished side effectsimpulsivity |
| spellingShingle | Agnieszka Nikiforuk Predrag Kalaba Marija Ilic Volker Korz Vladimir Dragačević Judith Wackerlig Thierry Langer Harald Höger Joanna Golebiowska Piotr Popik Gert Lubec A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats Frontiers in Behavioral Neuroscience cognitive flexibility novel DAT inhibitors cognitive enhancement diminished side effects impulsivity |
| title | A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats |
| title_full | A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats |
| title_fullStr | A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats |
| title_full_unstemmed | A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats |
| title_short | A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats |
| title_sort | novel dopamine transporter inhibitor ce 123 improves cognitive flexibility and maintains impulsivity in healthy male rats |
| topic | cognitive flexibility novel DAT inhibitors cognitive enhancement diminished side effects impulsivity |
| url | http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00222/full |
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