Allopregnanolone and ganaxolone increase the firing activity of dorsal raphe nucleus serotonergic neurons in female rats
Bibliographic record
Abstract
Accumulating evidence suggest a reciprocal interaction between neurosteroids, especially 5alpha-pregnan-3alpha-ol,20-one (3alpha,5alpha-THP, allopregnanolone), and the serotonergic (5-HT) system. Both 5-HT and neurosteroids seem to play an important role in the pathophysiology of major depression. We have previously shown that a 7-d treatment with 3alpha,5alpha-THP drastically increases the spontaneous firing activity of dorsal raphe nucleus (DRN) 5-HT neurons in female rats. This study was thus undertaken to better characterize this modulation and to assess the effects of ganaxolone, a synthetic analogue of 3alpha,5alpha-THP. Female rats received 50 microg/kg.d of 3alpha,5alpha-THP or ganaxolone for 3 and 7 days. Others received 3alpha,5alpha-THP concomitantly with the antiprogestin RU486 (50 microg/kg.d, each), which was also administered alone. Acute experiments were also carried out with a single injection of 3alpha,5alpha-THP (1 microg/kg). Finally, both 3alpha,5alpha-THP and ganaxolone (50 microg/kg.d) were administered along with the selective serotonin reuptake inhibitor (SSRI) citalopram (10 mg/kg.d). In-vivo extracellular unitary recordings of 5-HT neurons from the DRN, revealed that 3alpha,5alpha-THP and ganaxolone increased their firing activity after 3 and 7 d of treatment. A 7-d treatment with RU486 had the same effect. Furthermore, an increase could be seen as soon as after 30-60 min following a single injection with 3alpha,5alpha-THP. Interestingly, both 3alpha,5alpha-THP and ganaxolone prevented the citalopram-induced reduction in firing activity after 3-d treatments. These data demonstrate the ability of 3alpha,5alpha-THP and ganaxolone to positively modulate the firing activity of DRN 5-HT neurons in female rats. Moreover, these results suggest that these neuroactive steroids might represent interesting adjuvants in the treatment of mood disorders in female patients.
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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 | 0.000 | 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 | 0.001 | 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".