مدل سازی علائم روان پریشی و شناختی اختلالات عاطفی:نقص مهار مختل شده و آموزش معکوس نهفته در استرس واکنش موش
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|37044||2010||8 صفحه PDF||سفارش دهید||7459 کلمه|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Neurobiology of Learning and Memory, Volume 94, Issue 2, September 2010, Pages 145–152
Increased stress reactivity has repeatedly been reported in patients suffering from psychiatric diseases including schizophrenia and major depression. These disorders also have other symptoms in common, such as cognitive deficits and psychotic-like behavior. We have therefore investigated if increased stress reactivity is associated with these phenotypic endpoints in an animal model of affective disorders. The stress reactivity mouse model used in this study consists of three CD-1-derived mouse lines, that have been selectively bred for high (HR), intermediate (IR) or low (LR) stress reactivity. Male mice from these three breeding lines were subjected to a reversal learning task and latent inhibition (Li) was assessed using a conditioned taste aversion paradigm. Furthermore, as the dopaminergic system is involved in both Li and reversal learning, the dopamine 1 receptor (D1R), dopamine 2 receptor (D2R) and dopamine transporter (DAT) mRNA expression levels were assessed in relevant brain areas of these animals. The results demonstrate that HR mice show perseveration in the reversal learning task and have disrupted Li. Furthermore, compared to LR mice, HR mice have decreased D2R mRNA levels in the ventral tegmental area, as well as decreased D1R mRNA levels in the cingulate cortex, and an increased expression of D2R mRNA in the nucleus accumbens. Taken together, these results demonstrate that the HR mice display cognitive deficits associated with psychotic-like behavior, similar to those observed in patients suffering from schizophrenia and major depression and could be utilized in the search for better treatment strategies for these symptoms of psychiatric disorders.
Although many treatment strategies are available, major depression (MD) is not a fully treatable disorder (Holsboer and Ising, 2010 and Wong and Licinio, 2001). This particularly applies to the symptoms in the cognitive realm that often subside when the affective symptoms of the disease have successfully been treated (Reppermund et al., 2009 and Reppermund et al., 2007). Typical antidepressants also lack the capacity to treat the psychotic symptoms of major MD (Holtzheimer & Nemeroff, 2006). It is therefore of great importance to better understand the mechanisms underlying these cognitive deficits and psychotic symptoms and to explore new potential targets for their treatment. Drugs focusing on the dopaminergic system, such as atypical antipsychotics, have shown great promise in treating depressed patients who do not respond to typical antidepressants (Quintin & Thomas, 2004). Atypical antipsychotics are believed to exert their effect by increasing dopaminergic activity in the prefrontal cortex (PFC) implicating the dopaminergic system in these symptoms (Ichikawa et al., 2002, Kuroki et al., 1999 and Rollema et al., 1997). The dopaminergic system subserves an optimal neuronal function in the PFC (Cropley, Fujita, Innis, & Nathan, 2006), which plays a key role in executive functioning tasks (Carpenter et al., 2000, Petrides, 1994 and Robbins and Arnsten, 2009). Fittingly, executive functioning tasks are the cognitive tasks that depressed patients and schizophrenic patients display the most deficits in (Austin et al., 2001, Porter et al., 2003, Rabin et al., 2009, Reppermund et al., 2007, Reppermund et al., 2009 and Shirayama et al., 2009). Thus, it appears that psychotic MD and schizophrenia (SZ) share certain symptoms and possibly have similar underlying biological underpinnings causing these symptoms. It was therefore our aim to study these