A novel heterocyclic compound CE-104 enhances spatial working memory in the radial arm maze in rats and modulates the dopaminergic system / Aher Y.D., Subramaniyan S., Shanmugasundaram B., Sase A., Saroja S.R., Holy M., Höger H., Beryozkina T., Sitte H.H., Leban J.J., Lubec G. // Frontiers in Behavioral Neuroscience. - 2016. - V. 10, l. FEB.

ISSN:
16625153
Type:
Article
Abstract:
Various psychostimulants targeting monoamine neurotransmitter transporters (MATs) have been shown to rescue cognition in patients with neurological disorders and improve cognitive abilities in healthy subjects at low doses. Here, we examined the effects upon cognition of a chemically synthesized novel MAT inhibiting compound 2-(benzhydrylsulfinylmethyl)-4-methylthiazole (named as CE-104). The efficacy of CE-104 in blocking MAT [dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter] was determined using in vitro neurotransmitter uptake assay. The effect of the drug at low doses (1 and 10 mg/kg) on spatial memory was studied in male rats in the radial arm maze (RAM). Furthermore, the dopamine receptor and transporter complex levels of frontal cortex (FC) tissue of trained and untrained animals treated either with the drug or vehicle were quantified on blue native PAGE (BN-PAGE). The drug inhibited dopamine (IC50: 27.88 µM) and norepinephrine uptake (IC50: 160.40 µM), but had a negligible effect on SERT. In the RAM, both drug-dose groups improved spatial working memory during the performance phase of RAM as compared to vehicle. BN-PAGE Western blot quantification of dopamine receptor and transporter complexes revealed that D1, D2, D3, and DAT complexes were modulated due to training and by drug effects. The drug’s ability to block DAT and its influence on DAT and receptor complex levels in the FC is proposed as a possible mechanism for the observed learning and memory enhancement in the RAM. © 2016 Aher, Subramaniyan, Shanmugasundaram, Sase, Saroja, Holy, Höger, Beryozkina, Sitte, Leban and Lubec.
Author keywords:
CE-104; Cognitive enhancement; Dopamine receptor complexes; Dopamine transporter complexes; Dopamine uptake inhibitor; Monoamine neurotransmitter uptake inhibitor; Radial arm maze
Index keywords:
2 (benzhydrylsulfinylmethyl) 4 methylthiazole; dopamine; dopamine 1 receptor; dopamine 2 receptor; dopamine 3 receptor; dopamine receptor; dopamine transporter; noradrenalin; noradrenalin transporter;
DOI:
10.3389/fnbeh.2016.00020
Смотреть в Scopus:
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84960086433&doi=10.3389%2ffnbeh.2016.00020&partnerID=40&md5=42cef685eb40d3f135d125a78b0b799e
Соавторы в МНС:
Другие поля
Поле Значение
Art. No. 20
Link https://www.scopus.com/inward/record.uri?eid=2-s2.0-84960086433&doi=10.3389%2ffnbeh.2016.00020&partnerID=40&md5=42cef685eb40d3f135d125a78b0b799e
Affiliations Department of Pediatrics, Medical University of Vienna, Vienna, Austria; Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria; Core Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Himberg, Austria; Ural Federal University, Yekaterinburg, Russian Federation; Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria
Author Keywords CE-104; Cognitive enhancement; Dopamine receptor complexes; Dopamine transporter complexes; Dopamine uptake inhibitor; Monoamine neurotransmitter uptake inhibitor; Radial arm maze
Chemicals/CAS dopamine, 51-61-6, 62-31-7; noradrenalin, 1407-84-7, 51-41-2
Tradenames ce 104
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Correspondence Address Lubec, G.; Department of Pharmaceutical Chemistry, University of ViennaAustria; email: gert.lubec@univie.ac.at
Publisher Frontiers Research Foundation
Language of Original Document English
Abbreviated Source Title Front. Behav. Neurosci.
Source Scopus