The CB<sub>1</sub>Neutral Antagonist AM4113 Retains the Therapeutic Efficacy of the Inverse Agonist Rimonabant for Nicotine Dependence and Weight Loss with Better Psychiatric Tolerability
Bibliographic record
Abstract
BACKGROUND: neutral antagonist AM4113 on the abuse-related effects of nicotine and its effects on anxiety and depressive-like behavior in rats. METHODS: Rats were trained to self-administer nicotine under a fixed-ratio 5 or progressive-ratio schedules of reinforcement. A control group was trained to self-administer food. The acute/chronic effects of AM4113 pretreatment were evaluated on nicotine taking, motivation for nicotine, and cue-, nicotine priming- and yohimbine-induced reinstatement of nicotine-seeking. The effects of AM4113 in the basal firing and bursting activity of midbrain dopamine neurons were evaluated in a separate group of animals treated with nicotine. Anxiety/depression-like effects of AM4113 and rimonabant were evaluated 24h after chronic (21 days) pretreatment (0, 1, 3, and 10mg/kg, 1/d). RESULTS: AM4113 significantly attenuated nicotine taking, motivation for nicotine, as well as cue-, priming- and stress-induced reinstatement of nicotine-seeking behavior. These effects were accompanied by a decrease of the firing and burst rates in the ventral tegmental area dopamine neurons in response to nicotine. On the other hand, AM4113 pretreatment did not have effects on operant responding for food. Importantly, AM4113 did not have effects on anxiety and showed antidepressant-like effects. CONCLUSION: Our results indicate that AM4113 could be a promising therapeutic option for the prevention of relapse to nicotine-seeking while lacking anxiety/depression-like side effects.
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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 | 0.000 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".