Evidence for Sequence-Dependent and Reversible Nonspecific Effects of PS-Capped Antisense Treatment After Intracerebral Administration
Bibliographic record
Abstract
Phosphorothioate (PS)-capped phosphodiester (PE) oligodeoxynucleotides (ODNs) were used to determine whether the dopamine-dependent locomotor-stimulant effect of nicotine is mediated via a4 subunit-containing nicotinic receptors. To this end, rats received direct intraventral tegmental area infusion of a4 antisense via osmotic minipump, and their locomotor response to nicotine (0.2 mg/kg, s.c.) was tested. Eight antisense ODNs were screened, but only one inhibited nicotine-induced locomotion. This inhibition was reversible and selective, insofar as basal (saline) activity was unaffected, and a mismatch ODN was without effect. However, antisense treatment also caused sequence-dependent toxic effects, including neuronal degeneration in the ventral tegmental area, dopaminergic denervation, and weight loss. We conclude that despite previous reports, PS-capped PE-ODNs can cause severe neurotoxicity on chronic infusion into brain tissue. Moreover, sequence dependence and temporal reversibility, two generally accepted criteria of antisense action, may sometimes reflect the occurrence of toxic effects and resultant functional compensation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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".