Postnatal maternal deprivation and pubertal stress have additive effects on dopamine D2 receptor and CaMKII beta expression in the striatum
Bibliographic record
Abstract
The goal of this study was to determine whether two stressors commonly used to model aspects of neuropsychiatric disease in rats have an additive effect on striatal dopamine type 2 receptor (D2R) expression, a key player in the etiology of neuropsychiatric disease. Animals subjected to early postnatal stress show alterations in function of the dopaminergic system thought to be mediated by stress-induced glucocorticoid release. Subsequent stress during puberty is known to further impact the dopaminergic system and result in dopaminergic hyperactivity analogous to schizophrenia. We exposed rats to maternal deprivation (MD) during the second postnatal week, a time of active striatal development. A subset of these animals were then subjected to pubertal stress induced by immobilization. Both procedures are know to induce glucocorticoid release. At the conclusion of the MD protocol, we observed upregulation in the expression of D2R and of dopamine- and cAMP-regulated phosphoprotein 32-KD (DARPP-32; PPP1R1B), but not of D1R, calcium/calmodulin-dependent protein kinase II beta (CaMKIIβ), CaMKIIα or neurokinin B (NKB). Animals exposed to pubertal stress showed upregulation in expression of both D2R and CaMKIIβ. Furthermore, rats previously exposed to MD showed a much greater upregulation in CaMKIIβ expression, than animals only exposed to pubertal stress. These results support the two-hit hypothesis, indicating that such stressors have an additive effect. The main targets appear to be the D2R and the CaMKIIβ, the latter being an important member of the DR signalling pathway, both of which are associated with schizophrenia.
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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) | 0.001 | 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".