Bibliographic record
Abstract
The consequence of repeated cocaine exposure and prolonged abstinence on glutamate receptor expression in the nucleus accumbens has been extensively studied. However, the early effects of cocaine on NMDAR signaling remain unknown. NMDAR signaling depends on the subunit composition, subcellular localization, and the interaction with proteins at the postsynaptic density (PSD), where NMDARs and other proteins form supercomplexes that are responsible for the signaling pathways activated by NMDAR-induced Ca<sup>2+</sup> influx. Here, we investigated the effect of cocaine on NMDAR subunit composition and subcellular localization after both intraperitoneal non-contingent cocaine and response-contingent intravenous cocaine self-administration in mice. We found that repeated cocaine exposure, regardless of the route or contingency of drug administration, decreases NMDAR interactions with the PSD and synaptic lipid rafts in the accumbens shell and dorsal striatum. We provide evidence that cocaine triggers an early redistribution of NMDARs from synaptic to extrasynaptic sites, and that this adaptation has implications in the activation of downstream signaling pathways. Thus, consistent with a loss of NMDAR function, cocaine-induced ERK phosphorylation is attenuated. Because early NMDAR activity contributes to the initiation of lasting addiction-relevant neuroadaptations, these data may hold clues into cellular mechanisms responsible for the development of cocaine addiction.
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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 | 0.000 | 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) | 0.005 | 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 teacher head, 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".