A novel, multiple symptom model of obsessive-compulsive-like behaviors in animals.
BACKGROUND
Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors.


METHODS
Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood.


RESULTS
Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex.


CONCLUSIONS
This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.
Andersen
Susan L
SL
Laboratory of Developmental Neuropharmacology, McLean Hospital/Harvard Medical School, Belmont, Massachusetts 02478, USA. sandersen@mclean.harvard.edu
Greene-Colozzi
Emily A
EA
Sonntag
Kai C
KC
D000818:Animals; D000831:Animals, Newborn / Q000523:psychology*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects*; D001522:Behavior, Animal / Q000187:drug effects*; D002997:Clomipramine / Q000009:adverse effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000139:chemically induced / Q000378:metabolism / Q000523:psychology*; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2; D002997:Clomipramine