5-HT and NA Reuptake Inhibitors and Appetite Regulation: The Role of the Central 5-HT Network
Bibliographic record
Abstract
Brain serotonin (5-hydroxytryptamine; 5-HT) systems have been implicated in the leptin-independent neural regulation of appetite, as indicated by the anorectic effects of drugs that directly or indirectly stimulate postsynaptic 5-HT receptors. The identification of 5-HT subtype receptor functions in the regulation of feeding behavior and energy balance using genetic models has shed new light on the poorly understood area of leptin-independent appetite regulation. With the voluntary withdrawal of d-fenfluramine, which inhibits serotonin (5-HT) uptake and induces 5-HT release, due to primary pulmonary hypertension, research attention has been focused on the downstream pathways of central 5-HT subtype receptors, especially 5-HT2C receptors (5-HT2CRs), in the regulation of satiety. Central 5-HT systems which operate via 5- HT2CRs have a complex neural network, with certain neurons in the hypothalamus harboring appetite regulatory neuropeptides such as proopiomelanocortin (POMC) and corticosterone releasing hormone (CRH). The 5-HT drugs, which enhance 5-HT release via 5-HT2CR in the hypothalamus, induce the activation of hypothalamus-pituitary adrenal (HPA) axis as well as satiety. On the other hand, the selective 5-HT reuptake inhibitors (SSRIs) and 5-HT and noradrenalin reuptake inhibitors (SNRIs) induce satiety without stimulating the HPA axis. 5-HT2CR and 5-HT1BR substantially contribute to the anorexic effects of fenfluramine, whereas inactivation of 5-HT2CR enhances the effects of SSRIs so as to increase extracellular 5-HT in the brain and induce the appetite suppressing effects via 5-HT1BR. Moreover, SNRIs induce satiety independently of 5-HT2CRs and 5-HT1BRs. alpha-1 Adrenoceptors likely contribute to the appetite suppressing effects of SNRIs. Thus, the complex 5-HT network systems orchestrate leptin-independent central appetite regulation. Keywords: Inhibitors, Brain serotonin, 5-HT receptors, hypothalamus, fenfluramine, appetite regulation
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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 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".