AM 251 produces sustained reductions in food intake and body weight that are resistant to tolerance and conditioned taste aversion
Bibliographic record
Abstract
The cannabinoid 1 (CB(1)) receptor has been implicated in the regulation of food intake. Here, we examine the effect of the CB(1) receptor antagonist AM 251 on food intake and body weight over a prolonged period. Further, we examine whether AM 251 produces conditioned taste aversion (CTA) and if sustained antagonism at central receptors contributes to its anorectic effect. The effect of AM 251 of food intake and body weight was examined in daily (1 mg kg(-1)) and 5-day (5 mg kg(-1)) dosing schedules. Matching reductions in food intake and body weight were observed in both paradigms. A single administration of AM 251 (5 mg kg(-1)) significantly reduced food intake for 4 days. Tolerance to the anorectic effects of AM 251 did not develop in either dosing strategy. Active avoidance of AM 251 (3; 5 mg kg(-1), i.p.) was examined using a CTA assay. Rats showed no evidence of CTA associated with AM 251. We investigated the sustained effect of AM 251 (5 mg kg(-1), i.p.) on CB(1) receptors in the hypothalamus using Delta(9)-tetrahydrocannabinol (8 mg kg(-1), i.p.) induced hypothermia. AM 251 initially blocked hypothermia, but this effect was not seen 2 or 4 days later. The results demonstrate that smaller, or infrequent, administrations of AM 251 can produce sustained reductions in food intake and body weight in rat. Reductions in food intake were sustained longer than AM 251 antagonized the effects of a CB(1) receptor agonist in the hypothalamus, and occurred independently of CTA.
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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 | 0.000 |
| 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".