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 whether the rewarding actions of NMDA receptor antagonists (PCP, MK-801, CPP) are dopamine-dependent by measuring self-administration behavior with and without dopamine antagonist co-infusion into nucleus accumbens
This is a Dopamine Antagonist Co-infusion Self-Administration protocol using rat as the model organism. The procedure involves 6 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-press self-administration with PCP in nucleus accumbens shell • Establish lever-press self-administration with MK-801 in nucleus accumbens shell • Establish lever-press self-administration with CPP in nucleus accumbens shell
Primary readouts
Key equipment and reagents
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Rats are trained to lever-press with reinforcement of microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens
Note: This establishes that PCP has direct rewarding actions in the nucleus accumbens 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 with reinforcement of microinjections of dizocilpine (MK-801) directly into nucleus accumbens shell
Note: MK-801 blocks NMDA receptor function but not 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”
Separate group of rats trained to lever-press with reinforcement of microinjections of 3-((±)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP) directly into nucleus accumbens shell
Note: CPP blocks NMDA receptor function but not 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”
Test PCP, MK-801, and CPP at a slightly more dorsal and lateral site in the core of nucleus accumbens to determine regional specificity
Note: Each drug was ineffective or markedly less effective 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”
During self-administration of PCP, MK-801, or CPP into nucleus accumbens, co-infuse sulpiride at a dose that effectively blocks intracranial self-administration of nomifensine
Note: Sulpiride dose is validated by its ability to block nomifensine self-administration. Self-administration of NMDA antagonists was not altered by sulpiride co-infusion
“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 are trained to lever-press when PCP, MK-801, and CPP are each microinjected 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 whether the rewarding actions of NMDA receptor antagonists (PCP, MK-801, CPP) are dopamine-dependent by measuring self-administration behavior with and without dopamine antagonist co-infusion into nucleus accumbens
Objective
To assess whether the rewarding actions of NMDA receptor antagonists (PCP, MK-801, CPP) are dopamine-dependent by measuring self-administration behavior with and without dopamine antagonist co-infusion into nucleus accumbens
Subjects
From paperrat • Not specified • unknown • Not specified • Not specified
Cohort notes
From paperSeparate groups tested with different drugs
Establish lever-press self-administration with PCP in nucleus accumbens shell (Not specified)
Establish lever-press self-administration with MK-801 in nucleus accumbens shell (Not specified)
Establish lever-press self-administration with CPP in nucleus accumbens shell (Not specified)
Test drug effectiveness at nucleus accumbens core site (Not specified)
Lever-press response rates during self-administration of NMDA antagonists
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
Effect of sulpiride co-infusion on self-administration behavior
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
Self-administration behavior in frontal cortex versus 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
Lever-press response rates during self-administration of NMDA antagonists
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
Effect of sulpiride co-infusion on self-administration behavior
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
Self-administration behavior in frontal cortex versus 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
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-press response rates during self-administration of NMDA antagonists; Effect of sulpiride co-infusion on self-administration behavior; Regional specificity of drug reward (shell vs. core of nucleus accumbens); Self-administration behavior in frontal cortex versus nucleus accumbens.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Lever-press response rates during self-administration of NMDA antagonists, Effect of sulpiride co-infusion on self-administration behavior, Regional specificity of drug reward (shell vs. core of nucleus accumbens), Self-administration behavior in frontal cortex versus nucleus accumbens.
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
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