The selective 5-HT 6 receptor antagonist SLV has putative cognitive- and social interaction enhancing properties in rodent models of cognitive impairment

Autor: A.G. Foley, Kruse Cornelis G, M.A.W. van der Neut, M. van Drimmelen, E. Andriambeloson, N.M.W.J. de Bruin, Josephus H. M. Lange, Jos Prickaerts, M. van der Wetering, K.M. Wicke, M. de Haan, A. van Loevezijn, L. de Groote, Jennifer Venhorst
Přispěvatelé: Publica, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Cognitive Neuroscience
Experimental and Cognitive Psychology
Hippocampus
Rats
Sprague-Dawley
Mice
03 medical and health sciences
Behavioral Neuroscience
Cognition
0302 clinical medicine
Pregnancy
medicine
Animals
Hippocampus (mythology)
Cognitive Dysfunction
5-Hydroxytryptamine(6) (5-HT6)
Social behavior
Rats
Wistar
Maze Learning
Donepezil
Prepulse inhibition
Behavior
Animal
Prepulse Inhibition
Pyramidal Cells
Age Factors
Antagonist
Recognition
Psychology
Spontaneous alternation
Effective dose (pharmacology)
Rats
Mice
Inbred C57BL
030104 developmental biology
Inhibitory Postsynaptic Potentials
Social Perception
Prenatal Exposure Delayed Effects
Receptors
Serotonin
5-HT6 receptor
NMDA receptor
Female
Serotonin Antagonists
Psychology
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Zdroj: Neurobiology of Learning and Memory, 133, 100-117. Elsevier Science
ISSN: 1074-7427
Popis: In the present study, our aim was to investigate whether the novel highly selective 5-hydroxytryptamine(6) (5-HT6) receptor antagonist SLV can ameliorate impairments in cognition and social interaction with potential relevance for both schizophrenia and Alzheimer's disease (AD). SLV sub-chronically- treated Wistar rats reared in isolation showed significantly enhanced prepulse inhibition (PPI) and object recognition performance when compared to vehicle - treated rats. In the isolated rats, also a significant reduction in expression of hippocampal neural cell adhesion molecule polysialylation (NCAM-PSA) was found which was ameliorated following treatment with SLV (30 mg/kg). The social engagement deficit in rats exposed in utero (on gestational day 12.5) to valproic acid (VPA) was reversed by treatment with SLV (30 mg/kg). SLV (20 and 30 mg/kg, p.o.) fully reversed MK-801 - induced deficits in the ORT and also scopolamine - induced deficits in both the Object Recognition Task (ORT) and Object Location Task (OLT) in Wistar rats. In addition, a combination of sub-optimal doses of SLV and donepezil attenuated scopolamine-induced ORT deficits. Furthermore, SLV (10 mg/kg, p.o.) reversed spontaneous alternation deficits in the T-maze induced by MK-801 administration in Swiss mice and in aged C57131/6J mice. SLV additionally improved T-Maze spatial learning and passive avoidance learning in Sprague-Dawley rats with amyoid-beta (A beta) injections into the hippocampus. In contrast, no benefits were found with SLV or the tested reference compounds (donepezil and RVT-101) on cognitive performance of 12 months old Tg2576 mice. Also, in the social recognition task, an absence of cognitive enhancing properties was observed with SLV on "normal forgetting" in Wistar rats. Finally, analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) frequency recorded from pyramidal cells revealed a reduction in the presence of 1 mu M of SLV. In conclusion, SLV was investigated in several rodent animal models and found to be effective at a least effective dose (LED) of 20 mg/kg and 10 mg/kg (p.o.) in the rat and the mouse, respectively. (C) 2016 Elsevier Inc. All rights reserved.
Databáze: OpenAIRE
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