Measuring amphetamine‐induced dopamine release in humans: A comparative meta‐analysis of [<sup>11</sup>C]‐raclopride and [<sup>11</sup>C]‐(+)‐PHNO studies
Bibliographic record
Abstract
Abstract The radiotracers [ 11 C]‐raclopride and [ 11 C]‐(+)‐PHNO are commonly used to measure differences in amphetamine‐induced dopamine release between healthy persons and persons with neuropsychiatric diseases. As an agonist radiotracer, [ 11 C]‐(+)‐PHNO should theoretically be roughly 2.7 times more sensitive to displacement by endogenous dopamine than [ 11 C]raclopride. To date, only one study has been published comparing the sensitivity of these two radiotracers to amphetamine‐induced dopamine release in healthy persons. Unfortunately, conflicting findings in the literature suggests that the dose of amphetamine they employed (0.3 mg/kg, p.o.) may not reliably reduce [ 11 C]‐raclopride binding in the caudate. Thus, it is unclear whether the preponderance of evidence supports the theory that [ 11 C]‐(+)‐PHNO is more sensitive to displacement by amphetamine in humans than [ 11 C]‐raclopride. In order to clarify these issues, we conducted a comparative meta‐analysis summarizing the effects of amphetamine on [ 11 C]‐raclopride and [ 11 C]‐(+)‐PHNO binding in healthy humans. Our analysis indicates that amphetamine given at 0.3 mg/kg, p.o. does not reliably reduce [ 11 C]‐raclopride binding in the caudate. Second, the greater sensitivity of [ 11 C]‐(+)‐PHNO is evidenced at 0.5 mg/kg, p.o., but not at lower doses of amphetamine. Third, our analysis suggests that [ 11 C]‐(+)‐PHNO may be roughly 1.5 to 2.5 times more sensitive to displacement by amphetamine than [ 11 C]‐raclopride in healthy persons. We recommend that future displacement studies with these radiotracers employ 0.5 mg/kg, p.o. of amphetamine with a dose, post‐scan interval of at least 3 hr. Using this dose of amphetamine, [ 11 C]‐raclopride studies should employ at least n = 34 participants per group, while [ 11 C]‐(+)‐PHNO studies should employ at least n = 6 participants per group, in order to be sufficiently powered (80%) to detect changes in radiotracer binding within the caudate.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.012 | 0.003 |
| Bibliometrics | 0.003 | 0.006 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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; both teacher heads agree on what is shown here.
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".