Clozapine and dopamine D<sub>3</sub> receptor antisense reduce cocaine‐ and amphetamine‐regulated transcript expression in the rat nucleus accumbens shell
Why this work is in the frame
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Bibliographic record
Abstract
Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide highly expressed in the hypothalamus and nucleus accumbens. Hypothalamic CART has been associated with food intake and body weight control, but in the nucleus accumbens the role of CART remains elusive. New generations of antipsychotic drugs show a good efficacy over psychotic symptoms but they induce an important weight gain. The mechanism underlying this unexpected side effect is still unknown. The present results show, for the first time, that acute and chronic treatment with the atypical neuroleptic clozapine, but not the conventional neuroleptic haloperidol, reduced the expression of CART mRNA in the shell of the nucleus accumbens. CART mRNA is colocalized with both dopamine D(2) and D(3) receptor transcripts in the nucleus accumbens shell. However, a dopamine D(3) receptor, but not D(2), antisense oligonucleotide administration reduced CART expression in this brain area. These results suggest that the dopamine D(3) receptor, but not the D(2), is involved in the control of CART expression in the nucleus accumbens and that it may participate in the modulation of CART mRNA levels by clozapine. The modulation of CART, an anorexigenic neuropeptide, in the dopamine mesolimbic pathway may potentially play a role in dysregulated food intake induced by some antipsychotic drugs.
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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 it