Ghrelin, Cannabinoids, and Motivation: Increased Food Motivation on Progressive Ratio Paradigm Through MAGL/FAAH Inhibition in a Rat Model
Bibliographic record
Abstract
Ghrelin is a stomach derived hormone that is popularly known for its orexigenic properties.Ghrelin acts on its receptor (the GHS-R) in the hypothalamus and ventral tegmental area (VTA) to increase both homeostatic and non-homeostatic feeding, respectively.Endogenous cannabinoid system also produces feeding effects via the cannabinoid receptor in these regions.While there is evidence of ghrelin requiring the endogenous cannabinoid system to produce its effects in the hypothalamus, how they interact within the VTA is not fully understood.It is hypothesized that ghrelin may influence this system by stimulating the release of endocannabinoids from dopamine cells through its action on the GHS-R, via increased synthesis and accumulation of membrane bound cannabinoid enzymes.To investigate this, we conducted two experiments.In experiment 1, we used a progressive ratio paradigm to examine the behavioural effects of blocking cannabinoid catabolism on ghrelin induced motivated feeding behaviours by administering an intra-VTA infusion of MAGL and FAAH inhibitors (MJN110/PF-00457845), followed by a threshold dose of acylated ghrelin.In experiment 2, we examined the protein level of cannabinoid related enzymes in the VTA following an injection of ghrelin using western blotting.Our results show a significant increase in motivated feeding behaviours in rats that received both the MAGL/FAAH inhibitor cocktail and ghrelin via increased lever pressing.Interestingly, western blot analyses showed an increase in the cannabinoid degrading enzyme MAGL and a decrease in the cannabinoid synthesizing enzyme DAGL-a.Together, our results suggest ghrelin and the endogenous cannabinoid system may interact within the VTA to produce feeding behaviours.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".