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Record W1770207329 · doi:10.1136/bmj.h5411

Paroxetine and Study 329: what we already knew and when

2015· letter· en· W1770207329 on OpenAlexaff
Larry D. Sasich

Bibliographic record

VenueBMJ · 2015
Typeletter
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsCanadian Chlorine Chemistry Council
Fundersnot available
KeywordsMethyllycaconitineMecamylamineAcetylcholineNeuroscienceNicotinic agonistNicotinic AntagonistChemistryInhibitory postsynaptic potentialGlutamate receptorBiophysicsDepolarizationPostsynaptic potentialAcetylcholine receptorBiologyNicotinic acetylcholine receptorReceptorPharmacologyBiochemistry

Abstract

fetched live from OpenAlex

The effects of acetylcholine on both pyramidal neurons and interneurons in the area CA1 of the rat hippocampus were examined, using intracellular recording techniques in an in vitroslice preparation. In current-clamp mode, fast local application of acetylcholine (ACh) to the soma of inhibitory interneurons in stratum radiatum resulted in depolarization and rapid firing of action potentials. Under voltage-clamp, ACh produced fast, rapidly desensitizing inward currents that were insensitive to atropine but that were blocked by nanomolar concentrations of the nicotinic α7 receptor-selective antagonists α-bungarotoxin (αBgTx) and methyllycaconitine. Nicotinic receptor antagonists that are not selective for α7-containing receptors had little (mecamylamine) or no effect (dihydro-β-erythroidine) on the ACh-induced currents. Glutamate receptor antagonists had no effect on the ACh-evoked response, indicating that the current was not mediated by presynaptic facilitation of glutamate release. However, the current could be desensitized almost completely by bath superfusion with 100 nm nicotine. In contrast to those actions on interneurons, application of ACh to the soma of CA1 pyramidal cells did not produce a detectable current. Radioligand-binding experiments with [125I]-αBgTx demonstrated that stratum radiatum interneurons express α7-containing nAChRs, and in situhybridization revealed significant amounts of α7 mRNA. CA1 pyramidal cells did not show specific binding of [125I]-αBgTx and only low levels of α7 mRNA. These results suggest that, in addition to their proposed presynaptic role in modulating transmitter release, α7-containing nAChRs also may play a postsynaptic role in the excitation of hippocampal interneurons. By desensitizing these receptors, nicotine may disrupt this action and indirectly excite pyramidal neurons by reducing GABAergic inhibition.

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 imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Research integrity
Consensus categoriesnone
DomainCandidate signal: Reporting · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Commentary · Consensus signal: none
Teacher disagreement score0.999
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.003
Open science0.0000.000
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0030.001

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.

Opus teacher head0.030
GPT teacher head0.284
Teacher spread0.254 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

Study designNot applicable
DomainReporting
GenreCommentary

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".

Quick stats

Citations0
Published2015
Admission routes1
Has abstractyes

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