Atypical antipsychotics do not reverse prepulse inhibition deficits in acutely psychotic schizophrenia.

OBJECTIVES: To investigate the effects of atypical antipsychotics on prepulse inhibition, startle response and habituation in acutely psychotic patients with schizophrenia, and investigate whether prepulse inhibition deficit improvements are a result of the direct impact of atypical antipsychotics or improvements in antipsychotic-related symptoms. METHODS: Prepulse inhibition, habituation and acoustic startle response were evaluated in healthy control subjects and patients with schizophrenia (either unmedicated with antipsychotics at the time of hospitalization or medicated with atypical antipsychotics for ≥1 month before hospitalization). RESULTS: Data were analysed for 26 patients in the unmedicated group, 20 patients in the medicated group and 31 control subjects. Compared with controls, both medicated and unmedicated patients showed prepulse inhibition deficits; however, there were no significant differences between the two patient groups. Lower prepulse inhibition levels were correlated with higher levels of positive, negative, general and total scores on the Positive and Negative Syndrome Scale. CONCLUSIONS: These results suggest that effects of atypical antipsychotics on prepulse inhibition may not be evident when patients with schizophrenia are acutely symptomatic, and do not directly influence prepulse inhibition.

The effect of citalopram on chronic stress-induced depressive-like behavior in rats through GSK3ß/ß-catenin activation in the medial prefrontal cortex.

Antidepressant treatments enhance synaptic connectivity in stress-sensitive brain regions such as the medial prefrontal cortex (mPFC). The mPFC plays a key role in controlling cognition and emotion. While several signaling pathways are involved in this enhancement process, the exact mechanisms are not fully established. In the present study, we evaluated the role of the glycogen synthase kinase 3ß (GSK3ß)/ß-catenin signaling pathway in the antidepressant effect of citalopram in rats exposed to forced swim stress. The acute stress group received the classic, two-day variant of the forced swimming test (FST), whereas the chronic stress group received swim stress for 14 consecutive days. We found that rats exposed to acute swim stress showed depressive-like behaviors and expressed normal GSK3ß and ß-catenin levels in the mPFC. Chronic swim stress, also induced a significant behavior changes but was associated with decreased levels of phosphorylated GSK3ß and ß-catenin in the rat's mPFC. Chronic citalopram treatment alleviated these behavioral changes in chronically stressed rats and normalized the downregulation of GSK3ß/ß-catenin signaling. Our results suggest that GSK3ß/ß-catenin signaling plays an important role in chronic but not acute stress-related depression and contributes, at least in part, to the antidepressant effects of citalopram in distinct brain regions associated with mood regulation.

Quetiapine ameliorates anxiety-like behavior and cognitive impairments in stressed rats: implications for the treatment of posttraumatic stress disorder.

The purpose of this study was to determine preventive and protective effects of chronic orally administration with quetiapine (QUE) against anxiety-like behavior and cognitive impairments in rats exposed to the enhanced single prolonged stress (ESPS), an animal model that is used to study post-traumatic stress disorder (PTSD), and to detect changes in the expression of cortical phosphorylated p44/42 extracellular-regulated protein kinase (pERK1/2). Before or after exposure to ESPS paradigm, consisting of 2-h constraint, 20-min forced swimming, ether-induced loss of consciousness, and an electric foot shock, rats were given orally QUE (10 mg/kg daily) for 14 days. Animals were then tested in the open field (OF), elevated plus-maze (EPM), and Morris water maze (MWM). Brains were removed for immunohistochemical staining of pERK1/2. ESPS exposure resulted in pronounced anxiety-like behavior compared to unexposed animals. ESPS-exposed animals also displayed marked learning and spatial memory impairments. However, QUE treatment (both before and after ESPS exposure) significantly ameliorated anxiety-like behavior, learning and spatial memory impairments. ESPS also markedly reduced the expression of pERK1/2 in the prefrontal cortex, medial amygdala nucleus, and cingulate gyrus. Both before and after ESPS exposure QUE treatments significantly elevated the reduced pERK1/2 expression in the three brain regions. QUE has preventive and protective effects against stress-associated symptoms and the changes in pERK1/2 functions may be associated with the pathophysiology of traumatic stress and the therapeutic efficacy of anti-PTSD therapy.