A Novel Heterocyclic Compound CE-104 Enhances Spatial Working Memory in the Radial Arm Maze in Rats and Modulates the Dopaminergic System / Aher Yogesh D.,Subramaniyan Saraswathi,Shanmugasundaram Bharanidharan,Sase Ajinkya,Saroja Sivaprakasam R.,Holy Marion,Hoeger Harald,Beryozkina Tetyana,Sitte Harald H.,Leban Johann J.,Lubec Gert // FRONTIERS IN BEHAVIORAL NEUROSCIENCE. - 2016. - V. 10, l. .

ISSN/EISSN:

1662-5153 / нет данных

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 (SERI), 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 mu M) and norepinephrine uptake (ICE,0: 160.40 mu M), but had a negligible effect on SERI. 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.

Author keywords:

CE-104; cognitive enhancement; dopamine uptake inhibitor; monoamine neurotransmitter uptake inhibitor; radial arm maze; dopamine receptor complexes; dopamine transporter complexes PREFRONTAL CORTEX; COGNITIVE FUNCTION; MONOAMINE TRANSPORTER; UPDATE 2014; MODAFINIL; DRUGS; MICE; AMPHETAMINES; PERFORMANCE; RECEPTORS

DOI:

10.3389/fnbeh.2016.00020

Web of Science ID:

ISI:000370590100002

Соавторы в МНС:

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Другие поля

Поле	Значение
Month	FEB 22
Publisher	FRONTIERS MEDIA SA
Address	PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND
Language	English
Article-Number	20
Keywords-Plus	PREFRONTAL CORTEX; COGNITIVE FUNCTION; MONOAMINE TRANSPORTER; UPDATE 2014; MODAFINIL; DRUGS; MICE; AMPHETAMINES; PERFORMANCE; RECEPTORS
Research-Areas	Behavioral Sciences; Neurosciences \& Neurology
Web-of-Science-Categories	Behavioral Sciences; Neurosciences
Author-Email	gert.lubec@univie.ac.at
ORCID-Numbers	Lubec, Gert/0000-0002-6333-9461 Sitte, Harald/0000-0002-1339-7444
Number-of-Cited-References	54
Usage-Count-Since-2013	8
Journal-ISO	Front. Behav. Neurosci.
Doc-Delivery-Number	DE4HP