title: Ritualistic chewing behavior induced by mCPP in the rat is an animal model of obsessive compulsive disorder.
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.
authors: University of Tennessee at Chattanooga, Department of Biological and Environmental Sciences, 615 McCallie Avenue, Chattanooga, TN 37403, USA. dkreiss@colgate.edu
authors: Deborah S
authors: DS
authors: Kreiss
authors: Catherine F
authors: CF
authors: Coffman
authors: Nicholas R
authors: NR
authors: Fiacco
authors: Jason C
authors: JC
authors: Granger
authors: Bernadette M
authors: BM
authors: Helton
authors: Jennifer C
authors: JC
authors: Jackson
authors: Leonid V
authors: LV
authors: Kim
authors: Rishi S
authors: RS
authors: Mistry
authors: Tammie M
authors: TM
authors: Mizer
authors: Lolita V
authors: LV
authors: Palmer
authors: Jay A
authors: JA
authors: Vacca
authors: Stuart S
authors: SS
authors: Winkler
authors: Benjamin A
authors: BA
authors: Zimmer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002997:Clomipramine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008409:Mastication / Q000187:drug effects / Q000502:physiology; D008803:Mianserin / Q000494:pharmacology; D009771:Obsessive-Compulsive Disorder / Q000139:chemically induced* / Q000188:drug therapy / Q000523:psychology*; D010879:Piperazines / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000633:toxicity; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D002997:Clomipramine; D003975:Diazepam; D018492:Dopamine Antagonists; D016666:Fluvoxamine; D018757:GABA Modulators; D006220:Haloperidol; D008803:Mianserin; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C015068:1-(3-chlorophenyl)piperazine