Ex vivo [<sup>11</sup>C]‐(+)‐PHNO binding is unchanged in animal models displaying increased high‐affinity states of the D<sub>2</sub>receptor in vitro
Bibliographic record
Abstract
Dopamine (DA) D2 receptor supersensitivity has been linked to an increase in the density of the D2 high-affinity state as measured in vitro. The two- affinity-state model of the D2 receptor predicts that the ex vivo specific binding of [11C]-(+)-PHNO, an agonist radiotracer thought to bind selectively to the high-affinity state in vivo, should be increased in animal models that display in vitro increases in the proportion of receptors in the D2 high-affinity state. Here, we test this hypotheses by comparing the ex vivo SBR of [11C]-(+)-PHNO with that of the antagonist radiotracer [3H]-raclopride in three dopaminergically supersensitive rat models-AMPH-sensitized rats, rats withdrawn from chronic ethanol, and unilaterally 6-OHDA-lesioned rats-using ex vivo dual-radiotracer biodistribution studies. We find that in AMPH-sensitized rats and rats withdrawn from chronic ethanol treatment, models that exhibited approximately 4-fold increases in the D2 high-affinity state in vitro, the SBRs of [11C]-(+)-PHNO and [3H]-raclopride are unchanged relative to control rats. In unilaterally 6-OHDA-lesioned rats, we find that the increase in [11C]-(+)-PHNO SBR is no different than that observed for the antagonist radiotracer [3H]-raclopride (54% +/- 16% and 52% +/- 14%, respectively). In addition, the effect of acute AMPH pretreatment (4 mg/kg, i.v.) on the SBRs of [11C]-(+)-PHNO and [3H]-raclopride is equivalent in AMPH-sensitized (-38% +/- 12% and -36% +/- 8%, respectively) and in control rats (-40% +/- 11% and -38% +/- 7%). These data emphasize a significant discrepancy between in vitro and in vivo measures of D2 agonist binding, indicating that the two-affinity-state model of the D2 receptor may not apply veridically to living systems. The potential implications of this discrepancy are discussed.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".