Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00544566" target="_blank" >RIV/67985823:_____/21:00544566 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023752:_____/21:43920626 RIV/00216208:11110/21:10429722

Výsledek na webu

<a href="https://www.mdpi.com/2218-273X/11/7/1007" target="_blank" >https://www.mdpi.com/2218-273X/11/7/1007</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/biom11071007" target="_blank" >10.3390/biom11071007</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task

Popis výsledku v původním jazyce

Chronic sensitization to serotonin 1A and 7 receptors agonist 8-OH-DPAT induces compulsive checking and perseverative behavior. As such, it has been used to model obsessive-compulsive disorder (OCD)-like behavior in mice and rats. In this study, we tested spatial learning in the 8-OH-DPAT model of OCD and the effect of co-administration of memantine and riluzole—glutamate-modulating agents that have been shown to be effective in several clinical trials. Rats were tested in the active place avoidance task in the Carousel maze, where they learned to avoid the visually imperceptible shock sector. All rats were subcutaneously injected with 8-OH-DPAT (0.25 mg/kg) or saline (control group) during habituation. During acquisition, they were pretreated with riluzole (1 mg/kg), memantine (1 mg/kg), or saline solution 30 min before each session and injected with 8-OH-DPAT (“OH” groups) or saline (“saline” groups) right before the experiment. We found that repeated application of 8-OH-DPAT during both habituation and acquisition significantly increased locomotion, but it impaired the ability to avoid the shock sector. However, the application of 8-OH-DPAT in habituation had no impact on the learning process if discontinued in acquisition. Similarly, memantine and riluzole did not affect the measured parameters in the “saline” groups, but in the “OH” groups, they significantly increased locomotion. In addition, riluzole increased the number of entrances and decreased the maximum time avoided of the shock sector. We conclude that monotherapy with glutamate-modulating agents does not reduce but exacerbates cognitive symptoms in the animal model of OCD.

Název v anglickém jazyce

Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task

Popis výsledku anglicky

Chronic sensitization to serotonin 1A and 7 receptors agonist 8-OH-DPAT induces compulsive checking and perseverative behavior. As such, it has been used to model obsessive-compulsive disorder (OCD)-like behavior in mice and rats. In this study, we tested spatial learning in the 8-OH-DPAT model of OCD and the effect of co-administration of memantine and riluzole—glutamate-modulating agents that have been shown to be effective in several clinical trials. Rats were tested in the active place avoidance task in the Carousel maze, where they learned to avoid the visually imperceptible shock sector. All rats were subcutaneously injected with 8-OH-DPAT (0.25 mg/kg) or saline (control group) during habituation. During acquisition, they were pretreated with riluzole (1 mg/kg), memantine (1 mg/kg), or saline solution 30 min before each session and injected with 8-OH-DPAT (“OH” groups) or saline (“saline” groups) right before the experiment. We found that repeated application of 8-OH-DPAT during both habituation and acquisition significantly increased locomotion, but it impaired the ability to avoid the shock sector. However, the application of 8-OH-DPAT in habituation had no impact on the learning process if discontinued in acquisition. Similarly, memantine and riluzole did not affect the measured parameters in the “saline” groups, but in the “OH” groups, they significantly increased locomotion. In addition, riluzole increased the number of entrances and decreased the maximum time avoided of the shock sector. We conclude that monotherapy with glutamate-modulating agents does not reduce but exacerbates cognitive symptoms in the animal model of OCD.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biomolecules

ISSN

2218-273X

e-ISSN

2218-273X

Svazek periodika

11

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

14

Strana od-do

1007

Kód UT WoS článku

000676581000001

EID výsledku v databázi Scopus

2-s2.0-85109313299