Considerable attention is focused on defining the neurobiological mechanisms of the extinction of conditioned fear memory in

an effort to identify mechanisms that may hold clinical significance www.selleckchem.com/products/MDV3100.html for remediating aberrant fear memory. Serotonin modulates the acquisition and retention of conditioned emotional memory, and the serotonin 2A receptor (5HT2AR) may be one of the postsynaptic targets mediating such effects. Here we tested the hypothesis that the 5HT2AR regulates the consolidation and extinction of fear memory in male C57BL/6J mice. The influence of 5HT2ARs on memory consolidation was further confirmed with a novel object recognition task. With a trace fear conditioning paradigm, administration of the 5HT2AR agonist TCB-2 (1.0 mg/kg, i.p.) before the extinction test facilitated the acquisition of extinction of fear memory as compared to vehicle treatment. In contrast, administration of the 5HT2AR antagonist MDL 11,939 (0.5 mg/kg, i.p.) delayed the acquisition of extinction of fear memory. Further, the post-conditioning administration of TCB-2 enhanced contextual and cued fear memory, possibly by facilitating the consolidation of fear memory. Administration of TCB-2 also facilitated the acquisition

of extinction of fear memory in delay fear conditioned mice. Stimulation or blockade of 5HT2ARs did not affect the encoding or retrieval of conditioned fear memory. Finally, administration of TCB-2 right after training in an object recognition task enhanced the consolidation of object memory. These results suggest selleck chemical that stimulation of 5HT2ARs facilitates the consolidation and extinction of trace and delay cued fear memory and the consolidation of object memory. Blocking the 5HT2AR impairs the acquisition of fear memory extinction. The results support the view that serotonergic activation of the 5HT2AR provides an important modulatory influence Galeterone on circuits engaged during extinction learning. Taken together these results suggest that the 5HT2AR may be a potential therapeutic target for enhancing hippocampal and amygdala-dependent memory.

This article is part

of a Special Issue entitled ‘Cognitive Enhancers’. (C) 2012 Elsevier Ltd. All rights reserved.”
“Objective: To examine in a nonclinical sample of preadolescents the possibility that somatic and cognitive-affective depressive symptoms are differentially related with the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. Depression is a well-known risk factor for cardiovascular disease and mortality. Dysregulation of the ANS and the HPA axis have been proposed as underlying mechanisms. Several studies suggest that only a subset of the depression symptoms account for associations with cardiovascular prognosis. Methods: Self-reported somatic and cognitive-affective depressive symptoms were examined in relationship to heart rate variability (HRV), spontaneous baroreflex sensitivity (BRS), and the cortisol awakening response (CAR) in 2049 preadolescents (mean age = 11.