Detrimental effect of clomipramine on hippocampus-dependent learning in an animal model of obsessive-compulsive disorder induced by sensitization with d2/d3 agonist quinpirole
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
PubMed
27659555
DOI
10.1016/j.bbr.2016.09.042
PII: S0166-4328(16)30639-8
Knihovny.cz E-resources
- Keywords
- Animal model, Antidepressant, Antipsychotics, Obsessive-compulsive disorder, Quinpirole, Rat,
- MeSH
- Dopamine Agonists toxicity MeSH
- Analysis of Variance MeSH
- Serotonin Antagonists pharmacology MeSH
- Maze Learning drug effects MeSH
- Quinpirole toxicity MeSH
- Electroshock MeSH
- Hippocampus drug effects physiology MeSH
- Clomipramine therapeutic use MeSH
- Rats MeSH
- Locomotion drug effects MeSH
- Disease Models, Animal MeSH
- Obsessive-Compulsive Disorder chemically induced drug therapy MeSH
- Rats, Long-Evans MeSH
- Risperidone pharmacology MeSH
- Selective Serotonin Reuptake Inhibitors therapeutic use MeSH
- Avoidance Learning drug effects MeSH
- Escape Reaction drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- Dopamine Agonists MeSH
- Serotonin Antagonists MeSH
- Quinpirole MeSH
- Clomipramine MeSH
- Risperidone MeSH
- Serotonin Uptake Inhibitors MeSH
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.
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