Investigating the Dopaminergic and Glucocorticoid Systems as Underlying Mechanisms of Anhedonia
Bibliographic record
Abstract
Anhedonia, a severe deficit in reward processing, is an endophenotype of several neuropsychiatric disorders (APA, 2000) and increases susceptibility to depression (Atherton et al., 2015), substance abuse (Hatzigiakoumis et al., 2011), and suicidality (Winer et al., 2016). Recent literature suggests that anhedonia reflects a maladaptive interaction between reward circuitry and stress, the former being mediated by the mesolimbic dopamine (DA) system and the latter by the glucocorticoid system (Vrieze et al., 2013). The role of the DA system in the development and maintenance of anhedonia has been studied extensively, but little is known about the contribution of the glucocorticoid system to this process. The goal of the current study was to investigate the dopaminergic and glucocorticoid systems as underlying mechanisms of anhedonia using a validated rat test of anhedonia, the probabilistic reward task (PRT). In this task, rats learned to discriminate between two ambiguous tones for a sucrose reward. During testing, one lever was programmed to produce three times more reward than the other lever. Similar to healthy humans, rats develop a response bias toward the more frequently reinforced stimulus, regardless of which tone is presented. Consistent with prior literature, the response bias was enhanced following amphetamine- (AMPH) induced DA activation, and reduced following pramipexole- (PRAMI) induced DA inhibition. Additionally, a 21-day chronic mild stress (CMS) regimen attenuated the response bias in a subpopulation of animals relative to no stress controls. Finally, the glucocorticoid antagonist, mifepristone (MIFE), had no effect on the response bias relative to saline (SAL); however, the glucocorticoid agonist, dexamethasone (DEX), attenuated the response bias relative to both SAL and MIFE. These results confirm a role of DA in reward processing, and highlight an additional contribution of the glucocorticoid system in the mediation of this effect. Thus, it is plausible that chronic stress directly interferes with normal mesolimbic DA functioning, which leads to an overall impairment in reward responsiveness. These findings underscore the importance of treatment directed toward the DA and glucocorticoid systems, rather than the current SSRI treatment. Future studies on the etiology of anhedonia should carefully investigate the interaction of these systems in reward processing.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".