Source Paper
Rewarding Actions of Phencyclidine and Related Drugs in Nucleus Accumbens Shell and Frontal Cortex
William A. Carlezon,, Roy A. Wise
Journal of Neuroscience • 1996
Source Paper
William A. Carlezon,, Roy A. Wise
Journal of Neuroscience • 1996
Rats learned to lever-press when such behavior was reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens, indicating that the drug has direct rewarding actions in that region. Separate groups of rats learned to lever-press when reinforced with microinjections of dizocilpine (MK-801) or 3-((±)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP), drugs known to block NMDA receptor function but not dopamine uptake, into the same region. Each drug was ineffective or markedly less effective when injected at a slightly more dorsal and lateral site in the core of nucleus accumbens. Self-administration of PCP, MK-801, or CPP directly into nucleus accumbens was not altered by co-infusion of a dose of the dopamine antagonist sulpiride that effectively blocked intracranial self-administration of the dopamine uptake inhibitor nomifensine, suggesting that the rewarding actions of the NMDA receptor antagonists are not dopamine-dependent. Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex, a region previously associated with the rewarding actions of cocaine but not nomifensine. Thus nucleus accumbens and frontal cortex are each potential substrates for the rewarding properties of PCP and related drugs, and the ability of these drugs to disrupt NMDA receptor function seems sufficient to account for their rewarding actions. When considered with independent evidence, the present results suggest a model of drug reward within which the critical event is inhibition of medium spiny neurons in nucleus accumbens.
Objective: To assess regional specificity of drug reward by examining lever-pressing behavior reinforced by microinjections of NMDA receptor antagonists (PCP, MK-801, CPP) into nucleus accumbens core versus shell, and to determine whether rewarding actions are dopamine-dependent
This is a Intracranial Self-Administration in Nucleus Accumbens Core protocol using rat as the model organism. The procedure involves 10 procedural steps, 2 equipment items, 5 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
Establish lever-pressing behavior with PCP in nucleus accumbens shell • Test lever-pressing behavior with MK-801 in nucleus accumbens shell • Test lever-pressing behavior with CPP in nucleus accumbens shell
Primary readouts
Key equipment and reagents
Verified items
0
Direct vendor links
0
Use this page as an execution guide, then fall back to the source paper whenever you need exact exclusions, dosing details, or assay-specific caveats.
Confirm first
Use the page like this
Start here. The step list is optimized for running the experiment, with direct vendor links available inline when you need to source a cited item.
Rats are trained to lever-press with behavior reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens
Note: This establishes that PCP has direct rewarding actions in the shell region
“Rats learned to lever-press when such behavior was reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens”
Separate group of rats trained to lever-press when reinforced with microinjections of dizocilpine (MK-801) into the ventromedial (shell) region of nucleus accumbens
Note: MK-801 is an NMDA receptor antagonist that does not block dopamine uptake
“Separate groups of rats learned to lever-press when reinforced with microinjections of dizocilpine (MK-801) or 3-((±)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP), drugs known to block NMDA receptor function but not dopamine uptake, into the same region”
Separate group of rats trained to lever-press when reinforced with microinjections of CPP into the ventromedial (shell) region of nucleus accumbens
Note: CPP is an NMDA receptor antagonist that does not block dopamine uptake
“Separate groups of rats learned to lever-press when reinforced with microinjections of dizocilpine (MK-801) or 3-((±)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP), drugs known to block NMDA receptor function but not dopamine uptake, into the same region”
Test PCP microinjections at a slightly more dorsal and lateral site in the core of nucleus accumbens to assess regional specificity
Note: Each drug was ineffective or markedly less effective when injected at the core site compared to shell
“Each drug was ineffective or markedly less effective when injected at a slightly more dorsal and lateral site in the core of nucleus accumbens”
Test MK-801 microinjections at a slightly more dorsal and lateral site in the core of nucleus accumbens to assess regional specificity
Note: MK-801 was ineffective or markedly less effective when injected at the core site compared to shell
“Each drug was ineffective or markedly less effective when injected at a slightly more dorsal and lateral site in the core of nucleus accumbens”
Test CPP microinjections at a slightly more dorsal and lateral site in the core of nucleus accumbens to assess regional specificity
Note: CPP was ineffective or markedly less effective when injected at the core site compared to shell
“Each drug was ineffective or markedly less effective when injected at a slightly more dorsal and lateral site in the core of nucleus accumbens”
Co-infuse dopamine antagonist sulpiride (at a dose that effectively blocks nomifensine self-administration) with PCP, MK-801, or CPP microinjections into nucleus accumbens to determine if rewarding actions are dopamine-dependent
Note: Self-administration was not altered by sulpiride co-infusion, suggesting NMDA antagonist reward is not dopamine-dependent
“Self-administration of PCP, MK-801, or CPP directly into nucleus accumbens was not altered by co-infusion of a dose of the dopamine antagonist sulpiride that effectively blocked intracranial self-administration of the dopamine uptake inhibitor nomifensine”
Rats trained to lever-press when reinforced with microinjections of PCP directly into frontal cortex
Note: Frontal cortex is a region previously associated with rewarding actions of cocaine but not nomifensine
“Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex, a region previously associated with the rewarding actions of cocaine but not nomifensine”
Rats trained to lever-press when reinforced with microinjections of MK-801 directly into frontal cortex
Note: Frontal cortex is a region previously associated with rewarding actions of cocaine but not nomifensine
“Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex, a region previously associated with the rewarding actions of cocaine but not nomifensine”
Rats trained to lever-press when reinforced with microinjections of CPP directly into frontal cortex
Note: Frontal cortex is a region previously associated with rewarding actions of cocaine but not nomifensine
“Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex, a region previously associated with the rewarding actions of cocaine but not nomifensine”
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.
To assess regional specificity of drug reward by examining lever-pressing behavior reinforced by microinjections of NMDA receptor antagonists (PCP, MK-801, CPP) into nucleus accumbens core versus shell, and to determine whether rewarding actions are dopamine-dependent
Objective
To assess regional specificity of drug reward by examining lever-pressing behavior reinforced by microinjections of NMDA receptor antagonists (PCP, MK-801, CPP) into nucleus accumbens core versus shell, and to determine whether rewarding actions are dopamine-dependent
Subjects
From paperrat • Not specified • unknown • Not specified • Not specified
Cohort notes
From paperMultiple groups tested with different drug conditions
Establish lever-pressing behavior with PCP in nucleus accumbens shell (Not specified)
Test lever-pressing behavior with MK-801 in nucleus accumbens shell (Not specified)
Test lever-pressing behavior with CPP in nucleus accumbens shell (Not specified)
Test regional specificity - PCP in nucleus accumbens core (Not specified)
Lever-pressing behavior (frequency/rate)
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Regional specificity of drug reward (shell vs. core of nucleus accumbens)
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Effectiveness of drug reward in different brain regions (nucleus accumbens vs. frontal cortex)
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Dopamine-dependence of NMDA antagonist reward (measured by sulpiride co-infusion effects)
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Lever-pressing behavior (frequency/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
Regional specificity of drug reward (shell vs. core of nucleus accumbens)
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
Effectiveness of drug reward in different brain regions (nucleus accumbens vs. frontal cortex)
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-dependence of NMDA antagonist reward (measured by sulpiride co-infusion effects)
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 the provided text
Scoring or quantification
Quantify the primary readouts for this experiment: Lever-pressing behavior (frequency/rate); Regional specificity of drug reward (shell vs. core of nucleus accumbens); Effectiveness of drug reward in different brain regions (nucleus accumbens vs. frontal cortex); Dopamine-dependence of NMDA antagonist reward (measured by sulpiride co-infusion effects).
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Lever-pressing behavior (frequency/rate), Regional specificity of drug reward (shell vs. core of nucleus accumbens), Effectiveness of drug reward in different brain regions (nucleus accumbens vs. frontal cortex), Dopamine-dependence of NMDA antagonist reward (measured by sulpiride co-infusion effects).
Source links and direct wording from the methods section for validation and deeper review.
Citation
William A. Carlezon, et al. (1996). Rewarding Actions of Phencyclidine and Related Drugs in Nucleus Accumbens Shell and Frontal Cortex. Journal of Neuroscience
“”
“”
“”
“”
Direct vendor pages are linked from the protocol above. This section stays focused on the full comparison view and the prep checklist.
Gather these items before starting the experiment. Check off items as you prepare.
Not specified • Not specified • Not specified • Not specified
Not specified • Not specified • Not specified • Not specified
Not specified • Not specified • Not specified • Not specified
Not specified • Not specified • Not specified • Not specified
Not specified • Not specified • Not specified • Not specified
Not specified • Not specified • Not specified • Not specified
Not specified • Not specified • Not specified • Not specified
1 item with ReplicateScience direct pages
Estimated: $1,290.00
Use this section as the page quality checkpoint. It keeps section navigation, evidence access, readiness, and verification meaning in one place.
Current status surfaces were computed from experiment data updated Feb 28, 2026.
Source access
Jump back into the original paper or the methods evidence section when you need exact wording, exclusions, or method-specific caveats.
This protocol has structured steps plus evidence quotes, and is ready for canonical sync.
Steps
10
Evidence Quotes
17
Protocol Items
7
Linked Products
1
Canonical Sync
Pending
What this means
The completeness score reflects how much structured protocol data is present: steps, methods evidence, listed materials, linked products, and paper provenance.
Computed from the current experiment record updated Feb 28, 2026.
Canonical Sync shows whether a ConductGraph-backed protocol is available for this experiment route right now. It is a sync-status signal, not a claim that every downstream vendor link or step detail is perfect.
Steps
10
Evidence
17
Specific Products
1/1
Canonical Sync
Pending
What this score means
The verification score reflects evidence coverage, subject detail, paper provenance, step depth, and whether linked products resolve to specific item pages instead of generic searches.
Computed from the current experiment record updated Feb 28, 2026.
A page can have structured steps and still need review when evidence is thin, product links are generic, or canonical protocol coverage is still pending.