Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (<i>S</i>)-CE-123 on Mesocorticolimbic Dopamine System
Treatments for cognitive impairments associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder or narcolepsy, aim at modulating extracellular dopamine levels in the brain. CE-123 (5-((benzhydrylsulfinyl)methyl) thiazole) is a novel modafinil analog with improved sp...
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MDPI AG
2020-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/5/779 |
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| author | Claudia Sagheddu Nicholas Pintori Predrag Kalaba Vladimir Dragačević Gessica Piras Jana Lubec Nicola Simola Maria Antonietta De Luca Gert Lubec Marco Pistis |
| author_facet | Claudia Sagheddu Nicholas Pintori Predrag Kalaba Vladimir Dragačević Gessica Piras Jana Lubec Nicola Simola Maria Antonietta De Luca Gert Lubec Marco Pistis |
| author_sort | Claudia Sagheddu |
| collection | DOAJ |
| description | Treatments for cognitive impairments associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder or narcolepsy, aim at modulating extracellular dopamine levels in the brain. CE-123 (5-((benzhydrylsulfinyl)methyl) thiazole) is a novel modafinil analog with improved specificity and efficacy for dopamine transporter inhibition that improves cognitive and motivational processes in experimental animals. We studied the neuropharmacological and behavioral effects of the <i>S</i>-enantiomer of CE-123 ((<i>S</i>)-CE-123) and <i>R</i>-modafinil in cognitive- and reward-related brain areas of adult male rats. In vivo single unit recordings in anesthetized animals showed that (<i>S</i>)-CE-123, but not <i>R</i>-modafinil, dose-dependently (1.25 to 10 mg/kg i.v.) reduced firing of pyramidal neurons in the infralimbic/prelimbic (IL/PrL) cortex. Neither compound the affected firing activity of ventral tegmental area dopamine cells. In freely moving animals, (<i>S</i>)-CE-123 (10 mg/kg i.p.) increased extracellular dopamine levels in the IL/PrL, with different patterns when compared to <i>R</i>-modafinil (10 mg/kg i.p.); in the nucleus accumbens shell, a low and transitory increase of dopamine was observed only after (<i>S</i>)-CE-123. Neither (<i>S</i>)-CE-123 nor <i>R</i>-modafinil initiated the emission of 50-kHz ultrasonic vocalizations, a behavioral marker of positive affect and drug-mediated reward. Our data support previous reports of the procognitive effects of (<i>S</i>)-CE-123, and show a minor impact on reward-related dopaminergic areas. |
| first_indexed | 2024-03-10T19:46:27Z |
| format | Article |
| id | doaj.art-2bc9da98571c46c5b7965106ce4c0ddf |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T19:46:27Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-2bc9da98571c46c5b7965106ce4c0ddf2023-11-20T00:47:14ZengMDPI AGBiomolecules2218-273X2020-05-0110577910.3390/biom10050779Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (<i>S</i>)-CE-123 on Mesocorticolimbic Dopamine SystemClaudia Sagheddu0Nicholas Pintori1Predrag Kalaba2Vladimir Dragačević3Gessica Piras4Jana Lubec5Nicola Simola6Maria Antonietta De Luca7Gert Lubec8Marco Pistis9Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, ItalyDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, 1010 Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, 1010 Vienna, AustriaDepartment of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, ItalyDepartment of Neuroproteomics, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, ItalyDepartment of Neuroproteomics, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, ItalyTreatments for cognitive impairments associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder or narcolepsy, aim at modulating extracellular dopamine levels in the brain. CE-123 (5-((benzhydrylsulfinyl)methyl) thiazole) is a novel modafinil analog with improved specificity and efficacy for dopamine transporter inhibition that improves cognitive and motivational processes in experimental animals. We studied the neuropharmacological and behavioral effects of the <i>S</i>-enantiomer of CE-123 ((<i>S</i>)-CE-123) and <i>R</i>-modafinil in cognitive- and reward-related brain areas of adult male rats. In vivo single unit recordings in anesthetized animals showed that (<i>S</i>)-CE-123, but not <i>R</i>-modafinil, dose-dependently (1.25 to 10 mg/kg i.v.) reduced firing of pyramidal neurons in the infralimbic/prelimbic (IL/PrL) cortex. Neither compound the affected firing activity of ventral tegmental area dopamine cells. In freely moving animals, (<i>S</i>)-CE-123 (10 mg/kg i.p.) increased extracellular dopamine levels in the IL/PrL, with different patterns when compared to <i>R</i>-modafinil (10 mg/kg i.p.); in the nucleus accumbens shell, a low and transitory increase of dopamine was observed only after (<i>S</i>)-CE-123. Neither (<i>S</i>)-CE-123 nor <i>R</i>-modafinil initiated the emission of 50-kHz ultrasonic vocalizations, a behavioral marker of positive affect and drug-mediated reward. Our data support previous reports of the procognitive effects of (<i>S</i>)-CE-123, and show a minor impact on reward-related dopaminergic areas.https://www.mdpi.com/2218-273X/10/5/779cognitive enhancerprefrontal cortexdopaminedopamine transportermodafinilreward |
| spellingShingle | Claudia Sagheddu Nicholas Pintori Predrag Kalaba Vladimir Dragačević Gessica Piras Jana Lubec Nicola Simola Maria Antonietta De Luca Gert Lubec Marco Pistis Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (<i>S</i>)-CE-123 on Mesocorticolimbic Dopamine System Biomolecules cognitive enhancer prefrontal cortex dopamine dopamine transporter modafinil reward |
| title | Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (<i>S</i>)-CE-123 on Mesocorticolimbic Dopamine System |
| title_full | Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (<i>S</i>)-CE-123 on Mesocorticolimbic Dopamine System |
| title_fullStr | Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (<i>S</i>)-CE-123 on Mesocorticolimbic Dopamine System |
| title_full_unstemmed | Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (<i>S</i>)-CE-123 on Mesocorticolimbic Dopamine System |
| title_short | Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (<i>S</i>)-CE-123 on Mesocorticolimbic Dopamine System |
| title_sort | neurophysiological and neurochemical effects of the putative cognitive enhancer i s i ce 123 on mesocorticolimbic dopamine system |
| topic | cognitive enhancer prefrontal cortex dopamine dopamine transporter modafinil reward |
| url | https://www.mdpi.com/2218-273X/10/5/779 |
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