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      Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor

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      Neuropsychopharmacology
      Springer Nature

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          Abstract

          <p class="first" id="d956111e145">Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger <i>vs</i> smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression. </p>

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          Most cited references71

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          Effort-based decision-making in major depressive disorder: a translational model of motivational anhedonia.

          Anhedonia is a core feature of major depressive disorder (MDD), but the precise nature of anhedonic symptoms is unknown. Whereas anhedonia has traditionally been viewed as a deficit in the experience of pleasure, more recent evidence suggests that reduced anticipation and motivation may also be a core feature of this symptom. Here, we provide data from a study in MDD patients and healthy controls using a translational measure of reward motivation, the Effort Expenditure for Rewards Task (EEfRT or "effort"). This task offers subjects a series of trials where they may choose to expend more or less effort for the opportunity to win varying amounts of monetary rewards. We found that MDD patients were less willing to expend effort for rewards than controls. Additionally, we observed that patients were less able to effectively use information about magnitude and probability of rewards to guide their choice behavior. Finally, within the MDD patient group, duration of the current episode was a significant negative predictor of EEfRT task performance. These findings offer novel support for theoretical models proposing that anhedonia in MDD may reflect specific impairments in motivation and reward-based decision-making. PsycINFO Database Record (c) 2012 APA, all rights reserved.
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            Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse.

            Two G protein-coupled receptors have been identified that bind corticotropin-releasing factor (CRF) and urocortin (UCN) with high affinity. Hybridization histochemical methods were used to shed light on controversies concerning their localization in rat brain, and to provide normative distributional data in mouse, the standard model for genetic manipulation in mammals. The distribution of CRF-R1 mRNA in mouse was found to be fundamentally similar to that in rat, with expression predominating in the cerebral cortex, sensory relay nuclei, and in the cerebellum and its major afferents. Pronounced species differences in distribution were few, although more subtle variations in the relative strength of R1 expression were seen in several forebrain regions. CRF-R2 mRNA displayed comparable expression in rat and mouse brain, distinct from, and more restricted than that of CRF-R1. Major neuronal sites of CRF-R2 expression included aspects of the olfactory bulb, lateral septal nucleus, bed nucleus of the stria terminalis, ventromedial hypothalamic nucleus, medial and posterior cortical nuclei of the amygdala, ventral hippocampus, mesencephalic raphe nuclei, and novel localizations in the nucleus of the solitary tract and area postrema. Several sites of expression in the limbic forebrain were found to overlap partially with ones of androgen receptor expression. In pituitary, rat and mouse displayed CRF-R1 mRNA signal continuously over the intermediate lobe and over a subset of cells in the anterior lobe, whereas CRF-R2 transcripts were expressed mainly in the posterior lobe. The distinctive expression pattern of CRF-R2 mRNA identifies additional putative central sites of action for CRF and/or UCN. Constitutive expression of CRF-R2 mRNA in the nucleus of the solitary tract, and stress-inducible expression of CRF-R1 transcripts in the paraventricular nucleus may provide a basis for understanding documented effects of CRF-related peptides at a loci shown previously to lack a capacity for CRF-R expression or CRF binding. Other such "mismatches" remain to be reconciled. Copyright 2000 Wiley-Liss, Inc.
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              Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients.

              The possibility that hypersecretion of corticotropin-releasing factor (CRF) contributes to the hyperactivity of the hypothalamo-pituitary-adrenal axis observed in patients with major depression was investigated by measuring the concentration of this peptide in cerebrospinal fluid of normal healthy volunteers and in drug-free patients with DSM-III diagnoses of major depression, schizophrenia, or dementia. When compared to the controls and the other diagnostic groups, the patients with major depression showed significantly increased cerebrospinal fluid concentrations of CRF-like immunoreactivity; in 11 of the 23 depressed patients this immunoreactivity was greater than the highest value in the normal controls. These findings are concordant with the hypothesis that CRF hypersecretion is, at least in part, responsible for the hyperactivity of the hypothalamo-pituitary-adrenal axis characteristic of major depression.
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                Author and article information

                Journal
                Neuropsychopharmacology
                Neuropsychopharmacology
                Springer Nature
                0893-133X
                1740-634X
                February 24 2016
                February 24 2016
                : 41
                : 8
                : 2147-2159
                Article
                10.1038/npp.2016.15
                4908645
                26830960
                6726f58f-3ea1-4450-81af-d7e94ebd3ee4
                © 2016
                History

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