Dinner for Two: Digging into how Ghrelin and Endocannabinoid Systems Interact in the Ventral Tegmental Area to Regulate Non-Homeostatic Feeding
Bibliographic record
Abstract
Ghrelin, a hormone produced by the stomach during times of energy deficiency, potently enhances feeding by activating its receptor, the growth hormone secretagogue receptor (GHSR).In the brain, GHSRs are highly expressed within the hypothalamus (HYP) and ventral tegmental area (VTA), brain regions responsible for regulating hunger-driven and reward/motivated feeding, respectively.Interestingly, endogenous cannabinoids (i.e.endocannabinoids) induce similar feeding effects by stimulating cannabinoid receptors (CB-1Rs) in many of the same brain regions that highly express GHSRs, including the HYP and VTA.Recent evidence showed that ghrelin requires endocannabinoid signaling within the HYP to promote food intake.While independent GHSR or CB-1R activation within the VTA increases motivated feeding, it is not known whether the effects of ghrelin in the VTA are also dependent on the endocannabinoid system.This thesis aimed to determine if these systems interact within the VTA and to ascertain the extent and underlying mechanism by which CB-1R signaling may mediate the capacity of ghrelin to promote motivated feeding behaviours within this region.We determined that genetic disruption of GHSRs suppresses the gene expression of important endocannabinoid system proteins and lowers endocannabinoid levels within the VTA.Moreover, we demonstrated that pharmacological antagonism of VTA CB-1Rs attenuated the potent orexigenic and motivational capacity of intra-VTA ghrelin.Electrophysiological investigations indicated that CB-1R antagonism blocked the ability of ghrelin to promote excitatory drive to VTA dopamine neurons, but that ghrelin may independently and directly stimulate these neurons.Together, our data show that CB-1R signaling mediates ghrelininduced motivated feeding behaviours in the VTA.Our findings suggest that, as in the HYP and VTA, ghrelin and endocannabinoid systems may interact in all brain regions where their receptors are jointly expressed.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.029 | 0.010 |
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 source (direct Gemma or distilled Codex), 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".