AMPA receptors modulate enhanced dopamine neuronal activity induced by the combined administration of venlafaxine and brexpiprazole
Bibliographic record
Abstract
Abstract Addition of dopamine (DA)/serotonin (5-HT) partial agonists to 5-HT/norepinephrine (NE) reuptake inhibitors are commonly used to enhance the antidepressant response. The simultaneous inhibition of 5-HT and NE transporters with venlafaxine and its combination of brexpiprazole, which blocks the α2-adrenergic autoreceptor on NE terminals, could constitute a superior strategy. Anesthetized rats received venlafaxine and brexpiprazole for 2 and 14 days, then the firing activity of dorsal raphe nucleus 5-HT, locus coeruleus NE, and ventral tegmental area DA neurons were assessed. Net 5-HT and NE neurotransmissions were evaluated by assessing the tonic activation of 5-HT1A, and α1- and α2-adrenergic receptors in the hippocampus. The combination of brexpiprazole with venlafaxine resulted in normalized 5-HT and NE neuron activity, which occurred earlier than that with venlafaxine alone. A significant enhancement of the tonic activation of 5-HT1A receptors and α2-adrenoceptors in the hippocampus was observed following administration of the combination for 14 days. The combination more than doubled the number of DA neurons per electrode descent, after both 2 and 14 days, while this increase was observed only after 14 days of venlafaxine administration. This increase in population activity was prevented by NBQX, an AMPA receptor antagonist. In conclusion, early during administration, the combination of venlafaxine with brexpiprazole normalized firing activity of 5-HT and NE neurons, and increased the population activity of DA neurons through AMPA receptors. In the hippocampus, there was an overall increase in both 5-HT and NE transmissions. These results imply that this strategy could be a rapid-acting approach to treat depression.
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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) | 0.001 | 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".