Titel
A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats
Autor*in
Agnieszka Nikiforuk
Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences
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Abstract
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.
Stichwort
cognitive flexibilitynovel DAT inhibitorscognitive enhancementdiminished side effectsimpulsivity
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:860671
Erschienen in
Titel
Frontiers in Behavioral Neuroscience
Band
11
Verlag
Frontiers Media SA
Erscheinungsdatum
2017
Zugänglichkeit
Rechteangabe
© 2017 Nikiforuk, Kalaba, Ilic, Korz, Dragačević, Wackerlig, Langer, Höger, Golebiowska, Popik and Lubec

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