Source Paper
Involvement of the Dorsal Striatum in Cue-Controlled Cocaine Seeking
Louk J. M. J. Vanderschuren, Patricia Di Ciano, Barry J. Everitt
Journal of Neuroscience • 2005
Source Paper
Louk J. M. J. Vanderschuren, Patricia Di Ciano, Barry J. Everitt
Journal of Neuroscience • 2005
Through association with the interoceptive effects of drugs of abuse, neutral environmental stimuli can gain motivational properties themselves, becoming conditioned reinforcers that can evoke craving and relapse to drug seeking. Nucleus accumbens dopamine (DA) neurotransmission plays an important role in the reinforcing effect of cocaine itself, but, unlike nucleus accumbens glutamate, it seems not to mediate the conditioned reinforcing properties of cocaine-paired stimuli. Dorsal striatal DA transmission, in contrast, has been shown to be enhanced during cocaine seeking under a second-order schedule of reinforcement, which depends on the conditioned reinforcing properties of cocaine-associated stimuli. Therefore, the aim of the present study was to evaluate the role of DA and glutamate transmission in the dorsal striatum in cue-controlled cocaine seeking. Infusion of the DA receptor antagonist α-flupenthixol into the dorsal striatum decreased cocaine seeking under a second-order schedule of reinforcement. In addition, intradorsal striatal infusion of the AMPA/kainate (KA) receptor antagonist LY293558 (3 SR, 4a RS, 6 RS, 8a RS -6-[2-(i H -tetrazol-5-yl)ethyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroiso-quinoline-3-carboxylic acid), but not the NMDA receptor antagonist AP-5, also decreased cue-controlled cocaine seeking. These data show that stimulation of DA and AMPA/KA receptors in the dorsal striatum is critical for well established drug seeking that depends on the reinforcing effects of cocaine-associated stimuli. In addition, given the importance of the dorsal striatum in stimulus–response habit learning, these data suggest that the habitual or compulsive quality of persistent drug seeking depends on dorsal striatal mechanisms.
Objective: Evaluate the role of dopamine receptor antagonism in the dorsal striatum on cocaine seeking behavior under a second-order schedule of reinforcement, which depends on conditioned reinforcing properties of cocaine-associated stimuli
This is a Second-Order Schedule of Reinforcement with Dopamine Receptor Antagonism protocol using Not explicitly stated in provided text as the model organism. The procedure involves 7 procedural steps, 2 equipment items, 4 materials. Extracted from a 2005 paper published in Journal of Neuroscience.
Model and subjects
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Study window
Estimated timing pending
Core workflow
Establish cocaine seeking under second-order schedule • Infuse α-flupenthixol into dorsal striatum • Measure cocaine seeking behavior following α-flupenthixol infusion
Primary readouts
Key equipment and reagents
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Train subjects on second-order schedule of reinforcement with cocaine as reinforcer until behavior is well-established
Note: Schedule depends on conditioned reinforcing properties of cocaine-associated stimuli
“cocaine seeking under a second-order schedule of reinforcement, which depends on the conditioned reinforcing properties of cocaine-associated stimuli”
Administer dopamine receptor antagonist α-flupenthixol via intracerebral infusion into the dorsal striatum
Note: Dopamine receptor antagonist targeting dorsal striatal DA transmission
“Infusion of the DA receptor antagonist α-flupenthixol into the dorsal striatum decreased cocaine seeking under a second-order schedule”
Evaluate cocaine seeking behavior under second-order schedule following dopamine receptor antagonism
Note: Decreased cocaine seeking expected with dopamine receptor antagonism
“Infusion of the DA receptor antagonist α-flupenthixol into the dorsal striatum decreased cocaine seeking under a second-order schedule of reinforcement”
Administer AMPA/kainate receptor antagonist LY293558 via intracerebral infusion into the dorsal striatum
Note: AMPA/kainate receptor antagonist targeting glutamate transmission
“intradorsal striatal infusion of the AMPA/kainate (KA) receptor antagonist LY293558 also decreased cue-controlled cocaine seeking”
Evaluate cocaine seeking behavior under second-order schedule following AMPA/kainate receptor antagonism
Note: Decreased cocaine seeking expected with AMPA/kainate receptor antagonism
“intradorsal striatal infusion of the AMPA/kainate (KA) receptor antagonist LY293558 also decreased cue-controlled cocaine seeking”
Administer NMDA receptor antagonist AP-5 via intracerebral infusion into the dorsal striatum as control condition
Note: NMDA receptor antagonist used as control to test specificity of AMPA/kainate effects
“the NMDA receptor antagonist AP-5, also decreased cue-controlled cocaine seeking”
Evaluate cocaine seeking behavior under second-order schedule following NMDA receptor antagonism
Note: AP-5 used as control condition
“the NMDA receptor antagonist AP-5, also decreased cue-controlled cocaine seeking”
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.
Evaluate the role of dopamine receptor antagonism in the dorsal striatum on cocaine seeking behavior under a second-order schedule of reinforcement, which depends on conditioned reinforcing properties of cocaine-associated stimuli
Objective
Evaluate the role of dopamine receptor antagonism in the dorsal striatum on cocaine seeking behavior under a second-order schedule of reinforcement, which depends on conditioned reinforcing properties of cocaine-associated stimuli
Subjects
From paperNot explicitly stated in provided text • Not explicitly stated in provided text • unknown • Not explicitly stated in provided text • Not explicitly stated in provided text
Cohort notes
From paperNot explicitly stated in provided text
Establish cocaine seeking under second-order schedule (Not explicitly stated in provided text)
Infuse α-flupenthixol into dorsal striatum (Not explicitly stated in provided text)
Measure cocaine seeking behavior following α-flupenthixol infusion (Not explicitly stated in provided text)
Infuse LY293558 into dorsal striatum (Not explicitly stated in provided text)
Cocaine seeking behavior under second-order schedule of reinforcement
From paperNot explicitly stated in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Effect of dopamine receptor antagonism on cue-controlled cocaine seeking
From paperNot explicitly stated in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Effect of AMPA/kainate receptor antagonism on cue-controlled cocaine seeking
From paperNot explicitly stated in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Effect of NMDA receptor antagonism on cue-controlled cocaine seeking
From paperNot explicitly stated in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Cocaine seeking behavior under second-order schedule of reinforcement
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 dopamine receptor antagonism on cue-controlled cocaine seeking
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 AMPA/kainate receptor antagonism on cue-controlled cocaine seeking
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 NMDA receptor antagonism on cue-controlled cocaine seeking
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 explicitly stated in provided text
Scoring or quantification
Quantify the primary readouts for this experiment: Cocaine seeking behavior under second-order schedule of reinforcement; Effect of dopamine receptor antagonism on cue-controlled cocaine seeking; Effect of AMPA/kainate receptor antagonism on cue-controlled cocaine seeking; Effect of NMDA receptor antagonism on cue-controlled cocaine seeking.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Cocaine seeking behavior under second-order schedule of reinforcement, Effect of dopamine receptor antagonism on cue-controlled cocaine seeking, Effect of AMPA/kainate receptor antagonism on cue-controlled cocaine seeking, Effect of NMDA receptor antagonism on cue-controlled cocaine seeking.
Source links and direct wording from the methods section for validation and deeper review.
Citation
Louk J. M. J. Vanderschuren et al. (2005). Involvement of the Dorsal Striatum in Cue-Controlled Cocaine Seeking. Journal of Neuroscience
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