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.

• MeSH
• agonisté dopaminu toxicita   MeSH
• analýza rozptylu MeSH
• antagonisté serotoninu farmakologie   MeSH
• bludiště - učení účinky léků   MeSH
• chinpyrol toxicita   MeSH
• elektrický šok MeSH
• hipokampus účinky léků   fyziologie   MeSH
• klomipramin terapeutické užití   MeSH
• krysa rodu rattus MeSH
• lokomoce účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• obsedantně kompulzivní porucha chemicky indukované   farmakoterapie   MeSH
• potkani Long-Evans MeSH
• risperidon farmakologie   MeSH
• selektivní inhibitory zpětného vychytávání serotoninu terapeutické užití   MeSH
• učení vyhýbat se účinky léků   MeSH
• úniková reakce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH