Abstract
BackgroundObsessive–compulsive disorder (OCD) is a mental disease with heterogeneous behavioral phenotypes, including repetitive behaviors, anxiety, and impairments in cognitive functions. The brain regions related to the behavioral heterogeneity, however, are unknown.MethodsWe systematically examined the behavioral phenotypes of three OCD mouse models induced by pharmacological reagents [RU24969, 8-hydroxy-DPAT hydrobromide (8-OH-DPAT), and 1-(3-chlorophenyl) piperazine hydrochloride-99% (MCPP)], and compared the activated brain regions in each model, respectively.ResultsWe found that the mouse models presented distinct OCD-like behavioral traits. RU24969-treated mice exhibited repetitive circling, anxiety, and impairments in recognition memory. 8-OH-DPAT-treated mice exhibited excessive spray-induced grooming as well as impairments in recognition memory. MCPP-treated mice showed only excessive self-grooming. To determine the brain regions related to these distinct behavioral traits, we examined c-fos expression to indicate the neuronal activation in the brain. Our results showed that RU24969-treated mice exhibited increased c-fos expression in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), prelimbic cortex (PrL), infralimbic cortex (IL), nucleus accumbens (NAc), hypothalamus, bed nucleus of the stria terminalis, lateral division, intermediate part (BSTLD), and interstitial nucleus of the posterior limb of the anterior commissure, lateral part (IPACL), whereas in 8-OH-DPAT-treated mice showed increased c-fos expression in the ACC, PrL, IL, OFC, NAc shell, and hypothalamus. By contrast, MCPP did not induce higher c-fos expression in the cortex than control groups.ConclusionOur results indicate that different OCD mouse models exhibited distinct behavioral traits, which may be mediated by the activation of different brain regions.
Highlights
Obsessive–compulsive disorder (OCD) is a mental disorder mainly characterized by obsessive and compulsive behaviors
We systematically examined the behavioral phenotypes of three OCD mouse models induced by pharmacological reagents (RU24969, 8-OH-DPAT, and 1-(3-Chlorophenyl) piperazine hydrochloride-99% (MCPP)), and compared the activated brain regions in each model, respectively
Our results showed that different OCD mouse models exhibited distinct behavioral traits, which may be mediated by the activation of different brain regions
Summary
Obsessive–compulsive disorder (OCD) is a mental disorder mainly characterized by obsessive and compulsive behaviors. OCD is a highly heterogeneous disease, with which many patients experience anxiety and cognitive deficits . The symptoms vary widely among patients [5], and different dimensions of OCD symptoms may be caused by distinct neurobiological mechanisms [6]. Mataix-Cols et al used functional magnetic resonance imaging (fMRI) to measure neurological activity in patients with different symptom dimensions of OCD. They found that the activities of the bilateral ventromedial prefrontal regions and the right caudate nucleus were activated in patients with washing symptoms than in the control population. Obsessive–compulsive disorder (OCD) is a mental disease with heterogeneous behavioral phenotypes, including repetitive behaviors, anxiety, and impairments in cognitive functions. The brain regions related to the behavioral heterogeneity, are unknown
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