Influence of Oestrogenic Compounds on Monoamine Transporters in Rat Striatum
Bibliographic record
Abstract
Oestrogens have been reported to modulate rat membrane (DAT) and vesicular (VMAT(2)) dopamine transporters. A recent pilot study of postmenopausal women showed that chronic oestrogen replacement therapy increases striatal DAT. In the present study, we first investigated whether the oestrogen receptors alpha and beta mediate the effects of oestradiol on DAT and VMAT(2). Two days after ovariectomy, Sprague-Dawley rats were treated for 2 weeks with oestradiol or specific ligands for oestrogen receptor alpha, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) or oestrogen receptor beta, 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN). Ovariectomy caused a decrease in [(125)I]-3beta-(4-iodophenyl)-tropane-2beta-carboxylic acid isopropyl ester ([(125)I] RTI-121) specific binding to DAT transporters in the middle striatum compared to values for intact rats, and this was reversed by oestradiol replacement therapy. DPN, but not PPT, mimicked the effect of oestradiol. [(125)I] RTI-121 specific binding in the anterior and posterior striatum was not affected by ovariectomy or any of the drug treatments. Second, we investigated whether oestradiol increased DAT specific binding after a longer period of hormonal withdrawal (a model of hormonal withdrawal at menopause) and whether the selective oestrogen receptor modulators (SERMs), tamoxifen and raloxifene, could reproduce the oestradiol-induced increase of [(125)I] RTI-121 specific binding in long-term ovariectomised rats. Four months after ovariectomy, Sprague-Dawley rats were treated for 2 weeks with oestradiol, tamoxifen or raloxifene, and then killed. Ovariectomy decreased [(3)H] RTI-121 specific binding to DAT transporters in the middle striatum compared to values for intact rats. Treatment with oestradiol, tamoxifen and raloxifene reversed this effect. [(125)I] RTI-121 specific binding in anterior and posterior striatum was not affected by ovariectomy or treatment with oestrogen receptor ligands. In both experiments, neither ovariectomy nor the oestrogenic treatments modulated striatal [(3)H] tetrahydrobenazine specific binding to VMAT(2). Overall, these results suggest that oestrogen receptor beta mediates the oestradiol-induced increase of striatal DAT and that oestradiol can increase DAT density even after long-term steroid withdrawal. The results also support the premise that the SERMs tamoxifen and raloxifene exert oestrogenic agonist effects in the brain.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".