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

0473937 - FGÚ 2018 RIV NL eng J - Journal Article
Hatalová, Hana - Radostová, Dominika - Pištíková, Adéla - Valeš, Karel - Stuchlík, Aleš
Detrimental effect of clomipramine on hippocampus-dependent learning in an animal model of obsessive-compulsive disorder induced by sensitization with d2/d3 agonist quinpirole.
Behavioural Brain Research. Roč. 317, Jan 15 (2017), s. 210-217. ISSN 0166-4328. E-ISSN 1872-7549
R&D Projects: GA MZd(CZ) NV15-34524A; GA MŠMT(CZ) LH14053
Institutional support: RVO:67985823
Keywords : obsessive-compulsive disorder * antipsychotics * antidepressant * animal model * quinpirole * rat
OECD category: Neurosciences (including psychophysiology
Impact factor: 3.173, year: 2017

Quinpirole (QNP) sensitization is one of the commonly used animal models of obsessive-compulsive disorder (OCD). 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.
Permanent Link: http://hdl.handle.net/11104/0271040