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BACKGROUND Elevated phosphorylation of neurotrophin-regulated transcription factors, such as cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), in the hippocampus has been proposed as a common mediator of antidepressant (ADT) efficacy in otherwise naive rodents. The intracellular factors by which ADTs and glucocorticoids, causal(More)
Neurotransmitter- or neurotrophin-regulated intracellular signaling in the hippocampus is hypothesized to contribute to depression and antidepressant (ADT) efficacy. Extracellular signal-regulated kinase 1/2 (ERK1/2) is downstream of several receptor types and regulates transcriptional activity of many targets; ERK1/2 may thereby influence mood and affect.(More)
Alterations in multiple biological functions, such as transcription factor activity, are implicated in the neurobiology of depression, based primarily on the characterization of antidepressant efficacy in naïve rodents rather than on models that capture the protracted feelings of anhedonia and helplessness that typify depression. This unit presents rat and(More)
BACKGROUND Alterations in cellular survival and plasticity are implicated in the neurobiology of depression, based primarily on the characterization of antidepressant efficacy in naïve rodents rather than on models that capture the debilitating and protracted feelings of anhedonia and loss of motivation that are core features of depression. METHODS In(More)
Evaluation of the behavioral 'costs', such as effort expenditure relative to the benefits of obtaining reward, is a major determinant of goal-directed action. Neuroimaging evidence suggests that the human medial orbitofrontal cortex (mOFC) is involved in this calculation and thereby guides goal-directed and choice behavior, but this region's functional(More)
Stressor exposure biases decision-making strategies from those based on the relationship between actions and their consequences to others restricted by stimulus-response associations. Chronic stressor exposure also desensitizes glucocorticoid receptors (GR) and diminishes motivation to acquire food reinforcement, although causal relationships are largely(More)
The medial prefrontal cortex (mPFC) is known to regulate executive decisions and the expression of emotional memories. More specifically, the prelimbic cortex (PL) of the mPFC is implicated in driving emotional responses via downstream targets including the nucleus accumbens and amygdala, but mechanisms are yet to be fully understood. Therefore, we(More)
Adolescence is characterized by vulnerability to the development of neuropsychiatric disorders including drug addiction, as well as prefrontal cortical refinement that culminates in structural stability in adulthood. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, although(More)
BACKGROUND One of the most consistent morphologic findings in postmortem studies of brain tissue from depressed patients is a decrease in the number of glia in the prefrontal cortex. However, little is known about the mechanisms that contribute to this decrease in cell number. METHODS To address this question, we subjected adult rats to chronic stress, a(More)
A history of exposure to stressors may be a predisposing factor for developing posttraumatic stress disorder (PTSD) after trauma. Extinction of conditioned fear appears to be impaired in PTSD, but the consequences of prior stress or excess glucocorticoid exposure for extinction learning are not known. We report that prior chronic exposure to the stress(More)