The Effect of Typical and Atypical Antipsychotics on the MK-801 Induced Deficit in Behavioural Inhibition
Bibliographic record
Abstract
The non-competitive NMDA receptor antagonist (+)-5-methyl-10, 11-dihydro-5H-dibenzo [a, d,] cyclohepten-5-10-imine maleate (MK-801) has been shown to produce deficits in behavioral inhibition measured as the lack of extinction during operant procedures.As such, MK-801 has the potential to be used as a preclinical animal model of cognitive deficits that arise in schizophrenia.The present thesis sought to explore if typical and/or atypical antipsychotics have the ability to reverse deficits in behavioral inhibition (lack of extinction) seen following MK-801 administration.In addition, immunohistochemical labeling of pERK1/2 in the infralimbic cortex (IL) was examined after extinction lever pressing to determine the importance of the IL in mediating these behavioral changes.A dose-response curve revealed an extinction deficit following administration of 0.1 mg/kg of MK-801.The 0.1 mg/kg dose of MK-801 was also associated with a decrease in IL pERK1/2 labeling.Administration of the typical antipsychotic, Flupenthixol, did alter MK-801 effects on extinction bar pressing at the 0.25 mg/kg and 0.5 mg/kg doses.The highest dose of Flupenthixol also increased pERK1/2 labeling compared to MK-801 administration on its own.Administration of the atypical antipsychotic Clozapine did not alter extinction pressing following MK-801 and did not alter pERK1/2 labeling.Aripiprazole, given at 1 mg/kg, decreased MK-801 induced bar pressing to that of the saline control group but there were no differences in pERK1/2 labeling in the IL.The data suggest that MK-801 does induce deficits in behavior inhibition that may be dependent on dopamine neurotransmission.The increased pERK1/2 labeling in the IL following administration of 0.5 mg/kg of Flupenthixol highlights the importance of the IL in extinction learning.However, the IL !iii! is unlikely to be solely responsible for extinction learning as the 0.25 mg/kg dose of Flupenthixol and the 1 mg/kg dose of Aripiprazole decreased non-rewarded operant responding following MK-801 but did not alter IL pERK1/2 labeling.!
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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".