Abstract:
: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 not established. We show that a history of chronic exposure to the GR ligand corticosterone or acute posttraining GR blockade with RU38486 makes rodents less able to perform actions based on their consequences. Thus, optimal GR binding is necessary for the consolidation of new response-outcome learning. In contrast, medial prefrontal (but not striatal) BDNF can account for stress-related amotivation, in that selective medial prefrontal cortical Bdnf knockdown decreases break-point ratios in a progressive-ratio task. Knockdown also increases vulnerability to RU38486. Despite the role of BDNF in dendritic spine reorganization, deep-layer spine remodeling does not obviously parallel progressive-ratio response patterns, but treatment with the Na(+)-channel inhibitor riluzole reverses corticosteroid-induced motivational deficits and restores prefrontal BDNF expression after corticosterone. We argue that when prefrontal neurotrophin systems are compromised, and GR-mediated hypothalamic-pituitary-adrenal axis feedback is desensitized (as in the case of chronic stress hormone exposure), amotivation and inflexible maladaptive response strategies that contribute to stress-related mood disorders result.
journal_name
Proc Natl Acad Sci U S Aauthors
Gourley SL,Swanson AM,Jacobs AM,Howell JL,Mo M,Dileone RJ,Koleske AJ,Taylor JRdoi
10.1073/pnas.1208342109subject
Has Abstractpub_date
2012-12-11 00:00:00pages
20714-9issue
50eissn
0027-8424issn
1091-6490pii
1208342109journal_volume
109pub_type
杂志文章abstract::The capacity of a so-called male recombination (MR) chromosome in Drosophila melanogaster to generate mutations at 14 X-chromosome loci specifying visible phenotypes was investigated. Appreciable increases in mutation were found at three loci y, sn, and ras. Tests of represnetative mutants generated at each locus esta...
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