The Role of Nucleus Accumbens Dopamine D1-D2 Receptor Heteromer in the Phosphorylation of Cyclic-AMP Response Element-binding Protein
Bibliographic record
Abstract
Cocaine addiction is characterized by uncontrollable cocaine-craving, compulsive drug-seeking,and use despite devastating consequences to self and others. However, the neurobiological components underlying this disorder have not been fully elucidated. Our laboratory has previously demonstrated existence of dopamine D1-D2 receptor heteromers (D1-D2) in Nucleus Accumbens neurons capable of suppressing reinforcing effects of cocaine. Here we demonstrated that D1-D2 activation in a cell line or striatal neurons, with the agonist SKF83959, produced enhanced cyclic-AMP response element-binding protein (CREB) phosphorylation at the activating Ser133 residue. This effect was attenuated by blockade of intracellular Ca2+release, calcium calmodulin kinase II activation, or D1-D2 heteromer function. These findings demonstrate that D1-D2 activation is sufficient for inducing CREB Ser133 phosphorylation, which could be responsible for D1-D2-mediated reward attenuation through mediators further downstream, such as dynorphin. Overall, this study implicates CREB as an effector of D1-D2 activation, expanding our understanding of D1-D2 functional regulation and highlighting this signaling pathway as a potential target for treating cocaine addiction.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".