Netrin‐1 receptor in the ventral tegmental area is required for sensitization to amphetamine
Bibliographic record
Abstract
Fundamental to neural organization during development, the netrin-1 guidance cue and its receptor, deleted in colorectal cancer (DCC), continue to be expressed in the adult brain. We have shown recently that adult dcc heterozygous mice do not develop sensitization to the stimulant drug of abuse amphetamine (AMPH) and that repeated exposure to AMPH upregulates DCC expression in adult rats. This upregulation is selective to the ventral tegmental area (VTA), a site critical for the initiation of behavioral plasticity induced by stimulant drugs, and is glutamate-dependent. Here we demonstrate that the lack of AMPH-induced sensitization in dcc heterozygotes is associated with a failure of AMPH to upregulate DCC receptor expression in the VTA. Further, we show that, in wild-type mice, repeated AMPH induces increases in VTA expression of the dendritic spine-associated protein, spinophilin. Significantly, however, this effect is not observed in dcc heterozygotes. In parallel experiments conducted in adult rats, we show that VTA DCC receptor activation, at the time of AMPH pretreatment, is critical for sensitization to AMPH. Together, these results demonstrate that the DCC netrin-1 receptor, a protein traditionally known for its role in organizing brain development, plays a critical function in adult brain plasticity, possibly via orchestration of neuronal circuitry reorganization. We propose VTA DCC receptor signaling as a novel mechanism in the series of glutamate-dependent cellular processes that lead to enduring plasticity by drugs of abuse.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".