Source Paper
NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by dopamine
A Verma, B Moghaddam
Journal of Neuroscience • 1996
Source Paper
A Verma, B Moghaddam
Journal of Neuroscience • 1996
The present study was performed to assess the role of excitatory amino acid and dopamine receptors on associative functions of the prefrontal cortex (PFC) of the rat. Spatial delayed alternation was used as a PFC- sensitive cognitive task. In addition, in vivo microdialysis was used to assess the release of dopamine in the PFC. The noncompetitive NMDA antagonists ketamine (10–30 mg/kg) and MK-801 (0.1 and 0.5 mg/kg) dose- dependently impaired the spatial delayed alternation performance compared with the saline-treated control group. Administration of the dopamine antagonists raclopride (0.1 and 0.5 mg/kg), SCH-23390 (0.1 mg/kg), or haloperidol (0.1 mg/kg) was without a significant effect. However, haloperidol and raclopride (but not SCH-23390) reversed the disruptive effect of 30 mg/kg ketamine on spatial delayed alternation performance. Microdialysis studies revealed that this dose of ketamine preferentially increased the release of dopamine in the PFC compared with the striatum. These findings indicate that attenuation of glutamatergic neurotransmission at the NMDA receptor impairs PFC- dependent cognitive functions. Furthermore, activation of dopamine neurotransmission contributes, at least in part, to this impairment.
Objective: Assess the role of NMDA receptor antagonists and dopamine on prefrontal cortex function using spatial delayed alternation performance as a PFC-sensitive cognitive task measuring spatial working memory and associative functions
This is a Spatial Delayed Alternation Task protocol using rat as the model organism. The procedure involves 11 procedural steps, 2 equipment items, 6 materials. Extracted from a 1996 paper published in Journal of Neuroscience.
Model and subjects
rat • Not specified • unknown • Not specified • Not specified
Study window
Estimated timing pending
Core workflow
Baseline spatial delayed alternation testing • NMDA antagonist administration - Ketamine • NMDA antagonist administration - MK-801
Primary readouts
Key equipment and reagents
Verified items
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Establish baseline performance on the spatial delayed alternation task prior to drug administration
Note: Baseline performance must be established before drug testing
“Spatial delayed alternation was used as a PFC-sensitive cognitive task”
Administer ketamine at doses of 10, 20, or 30 mg/kg to assess dose-dependent effects on spatial delayed alternation performance
Note: Ketamine is a noncompetitive NMDA antagonist; dose-dependent impairment expected
“The noncompetitive NMDA antagonists ketamine (10–30 mg/kg) and MK-801 (0.1 and 0.5 mg/kg) dose-dependently impaired the spatial delayed alternation performance”
Administer MK-801 at doses of 0.1 or 0.5 mg/kg to assess dose-dependent effects on spatial delayed alternation performance
Note: MK-801 is a noncompetitive NMDA antagonist; dose-dependent impairment expected
“The noncompetitive NMDA antagonists ketamine (10–30 mg/kg) and MK-801 (0.1 and 0.5 mg/kg) dose-dependently impaired the spatial delayed alternation performance”
Administer raclopride at doses of 0.1 or 0.5 mg/kg to assess effects on spatial delayed alternation performance
Note: Dopamine antagonist alone showed no significant effect on performance
“Administration of the dopamine antagonists raclopride (0.1 and 0.5 mg/kg), SCH-23390 (0.1 mg/kg), or haloperidol (0.1 mg/kg) was without a significant effect”
Administer SCH-23390 at dose of 0.1 mg/kg to assess effects on spatial delayed alternation performance
Note: Dopamine antagonist alone showed no significant effect on performance
“Administration of the dopamine antagonists raclopride (0.1 and 0.5 mg/kg), SCH-23390 (0.1 mg/kg), or haloperidol (0.1 mg/kg) was without a significant effect”
Administer haloperidol at dose of 0.1 mg/kg to assess effects on spatial delayed alternation performance
Note: Dopamine antagonist alone showed no significant effect on performance
“Administration of the dopamine antagonists raclopride (0.1 and 0.5 mg/kg), SCH-23390 (0.1 mg/kg), or haloperidol (0.1 mg/kg) was without a significant effect”
Administer 30 mg/kg ketamine in combination with 0.1 mg/kg haloperidol to assess reversal of ketamine-induced impairment
Note: Haloperidol reversed the disruptive effect of 30 mg/kg ketamine on spatial delayed alternation performance
“haloperidol and raclopride (but not SCH-23390) reversed the disruptive effect of 30 mg/kg ketamine on spatial delayed alternation performance”
Administer 30 mg/kg ketamine in combination with 0.1 or 0.5 mg/kg raclopride to assess reversal of ketamine-induced impairment
Note: Raclopride reversed the disruptive effect of 30 mg/kg ketamine on spatial delayed alternation performance
“haloperidol and raclopride (but not SCH-23390) reversed the disruptive effect of 30 mg/kg ketamine on spatial delayed alternation performance”
Administer 30 mg/kg ketamine in combination with 0.1 mg/kg SCH-23390 to assess reversal of ketamine-induced impairment
Note: SCH-23390 did not reverse the disruptive effect of ketamine
“haloperidol and raclopride (but not SCH-23390) reversed the disruptive effect of 30 mg/kg ketamine on spatial delayed alternation performance”
Measure dopamine release in the prefrontal cortex and striatum following 30 mg/kg ketamine administration
Note: Ketamine preferentially increased dopamine release in PFC compared with striatum
“Microdialysis studies revealed that this dose of ketamine preferentially increased the release of dopamine in the PFC compared with the striatum”
Assess performance on spatial delayed alternation task following each drug administration condition
Note: Performance measured as primary outcome for all drug conditions
“Spatial delayed alternation was used as a PFC-sensitive cognitive task”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
Assess the role of NMDA receptor antagonists and dopamine on prefrontal cortex function using spatial delayed alternation performance as a PFC-sensitive cognitive task measuring spatial working memory and associative functions
Objective
Assess the role of NMDA receptor antagonists and dopamine on prefrontal cortex function using spatial delayed alternation performance as a PFC-sensitive cognitive task measuring spatial working memory and associative functions
Subjects
From paperrat • Not specified • unknown • Not specified • Not specified
Cohort notes
From paperNot specified
Baseline spatial delayed alternation testing (Not specified)
NMDA antagonist administration - Ketamine (Not specified)
NMDA antagonist administration - MK-801 (Not specified)
Dopamine antagonist administration - Raclopride (Not specified)
Spatial delayed alternation performance (accuracy/success rate)
From paperNot specified in methods section
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Dopamine release in prefrontal cortex measured by microdialysis
From paperNot specified in methods section
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Dopamine release in striatum measured by microdialysis
From paperNot specified in methods section
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Dose-dependent effects of NMDA antagonists on task performance
From paperNot specified in methods section
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Spatial delayed alternation performance (accuracy/success rate)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Dopamine release in prefrontal cortex measured by microdialysis
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Dopamine release in striatum measured by microdialysis
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Dose-dependent effects of NMDA antagonists on task performance
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not specified in methods section
Scoring or quantification
Quantify the primary readouts for this experiment: Spatial delayed alternation performance (accuracy/success rate); Dopamine release in prefrontal cortex measured by microdialysis; Dopamine release in striatum measured by microdialysis; Dose-dependent effects of NMDA antagonists on task performance.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Spatial delayed alternation performance (accuracy/success rate), Dopamine release in prefrontal cortex measured by microdialysis, Dopamine release in striatum measured by microdialysis, Dose-dependent effects of NMDA antagonists on task performance.
Source links and direct wording from the methods section for validation and deeper review.
Citation
A Verma et al. (1996). NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by dopamine. Journal of Neuroscience
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Evidence
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