Changes in 5-HT<sub>1A</sub> receptor binding and G-protein activation in the rat brain after estrogen treatment: comparison with tamoxifen and raloxifene
Bibliographic record
Abstract
Objective: It is thought that an imbalance in serotonergic neurotransmission may underlie many affective disorders. Thus, the serotonin-1A (5-HT 1A ) receptor is a target for antidepressant and neuroleptic drugs. It has been reported that estrogens modulate serotonergic neurotransmission. Therefore, we investigated the effect of long-term ovariectomy on 5-HT 1A receptor–specific binding and G-protein activation in the brain. Correction therapy with estradiol was compared with treatments using the selective estrogen receptor modulators tamoxifen and raloxifene. Methods: Four months after ovariectomy, Sprague–Dawley rats were treated with vehicle, 17β-estradiol (80 μg/kg), tamoxifen (1 mg/kg) or raloxifene (1 mg/kg) subcutaneously for 2 weeks. Specific binding to 5-HT 1A receptors was assessed by autoradiography of brain sections using the 5-HT 1A agonist [ 3 H]8-OH-DPAT. 5-HT 1A receptor stimulation was measured using R-(+)-8-OH-DPAT-stimulated [ 35 S]GTPγS-binding autoradiography. Results: Ovariectomy decreased uterine weight, which was corrected by estradiol; tamoxifen and raloxifene partially corrected this decrease. Hormonal withdrawal and replacement left [ 3 H]8-OH-DPAT-specific binding unchanged in the cortex. In contrast, ovariectomy induced a decrease in R-(+)-8-OH-DPAT-stimulated [ 35 S]GTPγS-specific binding in the cortex; this was corrected by estradiol but was not corrected significantly by tamoxifen or raloxifene. In the hippocampus, ovariectomy had no effect on [ 3 H]8-OH-DPAT-specific binding, whereas only 17β-estradiol treatment decreased this binding in a subregion of the CA3. Ovariectomy increased R-(+)-8-OH-DPAT-stimulated [ 35 S]GTPγS-specific binding in the dentate gyrus (but not in the CA1 or CA3); this was corrected by estradiol and raloxifene, but not by tamoxifen. In the dorsal raphe nucleus, ovariectomy increased [ 3 H]8-OH-DPAT-specific binding and R-(+)-8-OH-DPAT-stimulated [ 35 S]GTPγS-specific binding; estradiol corrected this increase, but this was not corrected significantly by tamoxifen or raloxifene. Conclusions: An overall stimulation by estradiol of 5-HT 1A receptor–specific binding and coupling was observed, decreasing raphe somatodendritic receptors and increasing cortical postsynaptic receptors.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".