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 the direct rewarding actions of phencyclidine (PCP) and related NMDA receptor antagonists (MK-801, CPP) by measuring lever-pressing behavior reinforced by microinjections into nucleus accumbens shell and frontal cortex
This is a Intracranial Self-Administration in Nucleus Accumbens Shell protocol using rat as the model organism. The procedure involves 7 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
Surgical implantation of microinjection cannulae • Operant conditioning training - PCP group • Operant conditioning training - MK-801 group
Primary readouts
Key equipment and reagents
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Implant microinjection cannulae targeting the ventromedial (shell) region of nucleus accumbens in rats
Note: Separate groups received implants targeting either nucleus accumbens shell or core, or frontal cortex
“Rats learned to lever-press when such behavior was reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens”
Train rats to lever-press with reinforcement of PCP microinjections into nucleus accumbens shell
Note: Rats learned lever-pressing behavior when reinforced with drug microinjections
“Rats learned to lever-press when such behavior was reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens”
Train separate group of rats to lever-press with reinforcement of MK-801 microinjections 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”
Train separate group of rats to lever-press with reinforcement of CPP microinjections 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”
Inject each drug (PCP, MK-801, CPP) at a slightly more dorsal and lateral site in the core of nucleus accumbens to test regional specificity
Note: Each drug was ineffective or markedly less effective when injected at 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 sulpiride (dopamine antagonist) with PCP, MK-801, or CPP into nucleus accumbens shell during self-administration sessions
Note: Sulpiride dose was one that effectively blocked self-administration of nomifensine (dopamine uptake inhibitor)
“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”
Microinject PCP, MK-801, and CPP directly into frontal cortex and measure lever-pressing behavior
Note: Frontal cortex was 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 the direct rewarding actions of phencyclidine (PCP) and related NMDA receptor antagonists (MK-801, CPP) by measuring lever-pressing behavior reinforced by microinjections into nucleus accumbens shell and frontal cortex
Objective
To assess the direct rewarding actions of phencyclidine (PCP) and related NMDA receptor antagonists (MK-801, CPP) by measuring lever-pressing behavior reinforced by microinjections into nucleus accumbens shell and frontal cortex
Subjects
From paperrat • Not specified • unknown • Not specified • Not specified
Cohort notes
From paperSeparate groups tested with different drugs (PCP, MK-801, CPP)
Surgical implantation of microinjection cannulae (Not specified)
Operant conditioning training - PCP group (Not specified)
Operant conditioning training - MK-801 group (Not specified)
Operant conditioning training - CPP group (Not specified)
Lever-pressing behavior (rate and frequency)
From paperNot specified in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Development of self-administration habits
From paperNot specified in 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 provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Dopamine-dependence of reward (measured by sulpiride co-infusion effects)
From paperNot specified in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Lever-pressing behavior (rate and frequency)
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
Development of self-administration habits
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
Dopamine-dependence of 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 provided text
Scoring or quantification
Quantify the primary readouts for this experiment: Lever-pressing behavior (rate and frequency); Development of self-administration habits; Regional specificity of drug reward (shell vs. core of nucleus accumbens); Dopamine-dependence of 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 (rate and frequency), Development of self-administration habits, Regional specificity of drug reward (shell vs. core of nucleus accumbens), Dopamine-dependence of 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
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