Detrimental effect of clomipramine on hippocampus-dependent learning in an animal model of obsessive-compulsive disorder induced by sensitization with d2/d3 agonist quinpirole

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F17%3A43915167" target="_blank" >RIV/00023752:_____/17:43915167 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/17:00473937

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0166432816306398" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0166432816306398</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbr.2016.09.042" target="_blank" >10.1016/j.bbr.2016.09.042</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Detrimental effect of clomipramine on hippocampus-dependent learning in an animal model of obsessive-compulsive disorder induced by sensitization with d2/d3 agonist quinpirole

Popis výsledku v původním jazyce

Quinpirole (QNP) sensitization is one of the commonly used animal models of obsessive-compulsive disorder (OCD). We have previously shown that QNP-sensitized animals display a robust cognitive flexibility deficit in an active place avoidance task with reversal in Carousel maze. This is in line with numerous human studies showing deficits in cognitive flexibility in OCD patients. Here we explored the effect of clomipramine, an effective OCD drug that attenuates compulsive checking in QNP, on sensitized rats in acquisition and reversal performances in an active place avoidance task. We found that the addition of clomipramine to QNP-sensitization impairs acquisition learning to a degree that reversal learning could not be tested. In a hippocampal-independent two-way active avoidance task clomipramine did not have an effect on acquisition learning in QNP-treated rats; suggesting that the detrimental effect of clomipramine is hippocampus based. We also tested the effect of risperidone in QNP-sensitized animals, which is not effective in OCD treatment. Risperidone also marginally impaired acquisition learning of QNP-sensitized animals, but not reversal. Moreover, we explored the effect of the augmentation of clomipramine treatment with risperidone in QNP-sensitized rats- a common step in treating SRI-unresponsive OCD patients. Only under this treatment regime animals were unimpaired in both acquisition and reversal learning. Augmentation of SRI with neuroleptics therefore could be beneficial for improving cognitive flexibility, and possibly be considered a first line of treatment in patients with reduced cognitive flexibility.

Název v anglickém jazyce

Detrimental effect of clomipramine on hippocampus-dependent learning in an animal model of obsessive-compulsive disorder induced by sensitization with d2/d3 agonist quinpirole

Popis výsledku anglicky

Quinpirole (QNP) sensitization is one of the commonly used animal models of obsessive-compulsive disorder (OCD). We have previously shown that QNP-sensitized animals display a robust cognitive flexibility deficit in an active place avoidance task with reversal in Carousel maze. This is in line with numerous human studies showing deficits in cognitive flexibility in OCD patients. Here we explored the effect of clomipramine, an effective OCD drug that attenuates compulsive checking in QNP, on sensitized rats in acquisition and reversal performances in an active place avoidance task. We found that the addition of clomipramine to QNP-sensitization impairs acquisition learning to a degree that reversal learning could not be tested. In a hippocampal-independent two-way active avoidance task clomipramine did not have an effect on acquisition learning in QNP-treated rats; suggesting that the detrimental effect of clomipramine is hippocampus based. We also tested the effect of risperidone in QNP-sensitized animals, which is not effective in OCD treatment. Risperidone also marginally impaired acquisition learning of QNP-sensitized animals, but not reversal. Moreover, we explored the effect of the augmentation of clomipramine treatment with risperidone in QNP-sensitized rats- a common step in treating SRI-unresponsive OCD patients. Only under this treatment regime animals were unimpaired in both acquisition and reversal learning. Augmentation of SRI with neuroleptics therefore could be beneficial for improving cognitive flexibility, and possibly be considered a first line of treatment in patients with reduced cognitive flexibility.

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

2017

Kód důvěrnosti údajů

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

Název periodika

Behavioural Brain Research

ISSN

0166-4328

e-ISSN

—

Svazek periodika

317

Číslo periodika v rámci svazku

January

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

210-217

Kód UT WoS článku

000389086700021

EID výsledku v databázi Scopus

2-s2.0-84988516610