1. Ritualistic chewing behavior induced by mCPP in the rat is an animal model of obsessive compulsive disorder.
- Author
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Kreiss DS, Coffman CF, Fiacco NR, Granger JC, Helton BM, Jackson JC, Kim LV, Mistry RS, Mizer TM, Palmer LV, Vacca JA, Winkler SS, and Zimmer BA
- Subjects
- Animals, Behavior, Animal drug effects, Behavior, Animal physiology, Clomipramine pharmacology, Diazepam pharmacology, Disease Models, Animal, Dopamine Antagonists pharmacology, Fluvoxamine pharmacology, GABA Modulators pharmacology, Haloperidol pharmacology, Male, Mastication drug effects, Mastication physiology, Mianserin pharmacology, Obsessive-Compulsive Disorder drug therapy, Piperazines toxicity, Rats, Rats, Sprague-Dawley, Serotonin Antagonists pharmacology, Serotonin Receptor Agonists toxicity, Selective Serotonin Reuptake Inhibitors pharmacology, Obsessive-Compulsive Disorder chemically induced, Obsessive-Compulsive Disorder psychology
- Abstract
Obsessive Compulsive Disorder (OCD) is characterized by recurrent, anxiety-producing thoughts accompanied by unwanted, overwhelming urges to perform ritualistic behaviors. Pharmacological treatments for this disorder (serotonin uptake inhibitors) are problematic because there is a 6-8 week delayed onset and half of the patients do not adequately respond. The present study evaluated whether Ritualistic Chewing Behaviors (RCBs) induced by the serotonin agonist mCPP in the rat is a behavioral model for OCD. The effects upon the RCBs induced by mCPP (1 mg/kg) were evaluated following treatments with either the serotonin antagonist mianserin (3 mg/kg), the dopamine antagonist haloperidol (1 mg/kg), the GABA modulator diazepam (10 mg/kg), or the serotonin uptake inhibitors clomipramine and fluvoxamine (15 mg/kg). The response to mCPP was blocked by acute treatment with mianserin, but not with acute haloperidol or diazepam. Further experiments revealed that the effects of mCPP were blocked by chronic, but not acute, treatment with clomipramine and fluvoxamine. A time-course demonstrated that 14 days of chronic treatment were required for blockade of the mCPP-evoked response. The current study demonstrates that mCPP-evoked RCBs may be a rodent model for OCD that can be used to predict the clinical efficacy and time course of novel OCD treatment. Future investigations may be able to use the current model as a tool for bench-marking corresponding changes in other measures of neurological activity that may provide insight into the mechanisms underlying OCD., (Copyright © 2013. Published by Elsevier Inc.)
- Published
- 2013
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