Bidirectional regulation of dopamine D2 and neurotensin NTS1 receptors in dopamine neurons
Bibliographic record
Abstract
Several lines of evidence suggest a close association between dopamine (DA) and neurotensin (NT) systems in the CNS. Indeed, in the rodent brain, abundant NT-containing fibres are found in DA-rich areas such as the ventral tegmental area and substantia nigra. Moreover, it has been shown in vivo that NT, acting through its high-affinity receptor (NTS1), reduces the physiological and behavioural effects of DA D2 receptor (D2R) activation, a critical autoreceptor feedback system regulating DA neurotransmission. However, the mechanism of this interaction is still elusive. The aim of our study was thus to reproduce in vitro the interaction between D2R and NTS1, and then to characterize the mechanisms implicated. We used a primary culture model of DA neurons prepared from transgenic mice expressing green fluorescent protein under the control of the tyrosine hydroxylase promoter. In these cultures, DA neurons endogenously express both D2R and NTS1. Using electrophysiological recordings, we show that activation of D2R directly inhibits the firing rate of DA neurons. In addition, we find that NT, acting through a NTS1-like receptor, is able to reduce D2R autoreceptor function independently of its ability to enhance DA neuron firing, and that this interaction occurs through a protein kinase C- and Ca(2+)-dependent mechanism. Furthermore, prior activation of D2R reduces the ability of NTS1 to induce intracellular Ca(2+) mobilization. Our findings provide evidence for bidirectional interaction between D2R and NTS1 in DA neurons, a regulatory mechanism that could play a key role in the control of the activity of these neurons.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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; 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".