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, however, are unknown. We 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. We 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. Our results indicate that different OCD mouse models exhibited distinct behavioral traits, which may be mediated by the activation of different brain regions.

中文翻译：

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强迫症小鼠模型中不同的行为特征和相关的大脑区域

强迫症（OCD）是一种具有异质行为表型的精神疾病，包括重复行为、焦虑和认知功能障碍。然而，与行为异质性相关的大脑区域是未知的。我们系统地检查了由药理试剂 [RU24969、8-羟基-DPAT 氢溴酸盐 (8-OH-DPAT) 和 1-(3-氯苯基) 哌嗪盐酸盐-99% (MCPP)] 诱导的三种 OCD 小鼠模型的行为表型，并分别比较了每个模型中激活的大脑区域。我们发现小鼠模型呈现出明显的强迫症样行为特征。RU24969 治疗的小鼠表现出重复的转圈、焦虑和识别记忆障碍。8-OH-DPAT 处理的小鼠表现出过度的喷雾诱导的梳理以及识别记忆的损害。MCPP 处理的小鼠仅表现出过度的自我修饰。为了确定与这些不同行为特征相关的大脑区域，我们检查了 c-fos 表达以指示大脑中的神经元激活。我们的研究结果表明，RU24969 处理的小鼠在眶额皮质 (OFC)、前扣带皮层 (ACC)、前肢皮质 (PrL)、下边缘皮质 (IL)、伏隔核 (NAc)、下丘脑、床中表现出 c-fos 表达增加终纹核、外侧分裂、中间部分 (BSTLD) 和前连合后肢的间质核、外侧部分 (IPACL)，而在 8-OH-DPAT 处理的小鼠中，c-fos 表达增加ACC、PrL、IL、OFC、NAc 壳和下丘脑。相比之下，MCPP 并未在皮层中诱导比对照组更高的 c-fos 表达。