Source Paper
Glutamate Release in the Nucleus Accumbens Core Is Necessary for Heroin Seeking
Ryan T. LaLumiere, Peter W. Kalivas
Journal of Neuroscience • 2008
Source Paper
Ryan T. LaLumiere, Peter W. Kalivas
Journal of Neuroscience • 2008
Long-term changes in glutamate transmission in the nucleus accumbens core (NAcore) contribute to the reinstatement of drug seeking after extinction of cocaine self-administration. Whether similar adaptations in glutamate transmission occur during heroin and cue-induced reinstatement of heroin seeking is unknown. After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training, heroin seeking was induced by a noncontingent injection of heroin or by presentation of light/tone cues previously paired with heroin infusions. Microdialysis was conducted in the NAcore during reinstatement of heroin seeking in animals extinguished from heroin self-administration or in subjects receiving parallel (yoked) noncontingent saline or heroin. Reinstatement by either heroin or cue increased extracellular glutamate in the NAcore in the self-administration group, but no increase was elicited during heroin-induced reinstatement in the yoked control groups. The increase in glutamate during heroin-induced drug seeking was abolished by inhibiting synaptic transmission in the NAcore with tetrodotoxin or by inhibiting glutamatergic afferents to the NAcore from the prelimbic cortex. Supporting critical involvement of glutamate release, heroin seeking induced by cue or heroin was blocked by inhibiting AMPA/kainate glutamate receptors in the NAcore. Interestingly, although a heroin-priming injection increased dopamine equally in animals trained to self-administer heroin and in yoked-saline subjects, inhibition of dopamine receptors in the NAcore also blocked heroin- and cue-induced drug seeking. Together, these findings show that recruitment of the glutamatergic projection from the prelimbic cortex to NAcore is necessary to initiate the reinstatement of heroin seeking.
Objective: To determine whether glutamate release in the nucleus accumbens core is necessary for heroin-induced reinstatement of drug seeking after extinction from heroin self-administration
This is a Heroin-Induced Reinstatement protocol using Not explicitly stated in provided text as the model organism. The procedure involves 9 procedural steps, 1 equipment items, 5 materials. Extracted from a 2008 paper published in Journal of Neuroscience.
Model and subjects
Not explicitly stated in provided text • Not explicitly stated in provided text • unknown • Not explicitly stated in provided text • Not explicitly stated in provided text
Study window
~2 week study window
Core workflow
Heroin self-administration training • Extinction training • Heroin-induced reinstatement testing
Primary readouts
Key equipment and reagents
Verified items
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Animals were trained to self-administer heroin
Note: Initial training phase before extinction
“After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training”
Animals underwent extinction training to reduce heroin seeking after self-administration training
Note: Conducted after heroin self-administration training
“After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training”
Heroin seeking was induced by a noncontingent injection of heroin in animals previously extinguished from heroin self-administration
Note: Microdialysis conducted during this phase to measure glutamate changes
“heroin seeking was induced by a noncontingent injection of heroin or by presentation of light/tone cues previously paired with heroin infusions”
Heroin seeking was induced by presentation of light and tone cues previously paired with heroin infusions
Note: Conducted in parallel with heroin-induced reinstatement testing
“heroin seeking was induced by a noncontingent injection of heroin or by presentation of light/tone cues previously paired with heroin infusions”
Parallel groups received noncontingent saline or heroin injections while undergoing microdialysis
Note: Control groups to compare glutamate responses between self-administration trained and yoked animals
“Microdialysis was conducted in the NAcore during reinstatement of heroin seeking in animals extinguished from heroin self-administration or in subjects receiving parallel (yoked) noncontingent saline or heroin”
Synaptic transmission in the nucleus accumbens core was inhibited with tetrodotoxin during heroin-induced reinstatement
Note: To test whether synaptic transmission is necessary for glutamate increase during heroin seeking
“increase in glutamate during heroin-induced drug seeking was abolished by inhibiting synaptic transmission in the NAcore with tetrodotoxin”
Glutamatergic afferents to the nucleus accumbens core from the prelimbic cortex were inhibited during reinstatement testing
Note: To test whether prelimbic cortex glutamate projection is necessary for heroin seeking reinstatement
“increase in glutamate during heroin-induced drug seeking was abolished by inhibiting glutamatergic afferents to the NAcore from the prelimbic cortex”
AMPA/kainate glutamate receptors in the nucleus accumbens core were inhibited during heroin and cue-induced reinstatement
Note: To test whether glutamate receptor activation is necessary for heroin seeking
“heroin seeking induced by cue or heroin was blocked by inhibiting AMPA/kainate glutamate receptors in the NAcore”
Dopamine receptors in the nucleus accumbens core were inhibited during heroin and cue-induced reinstatement
Note: To test role of dopamine in heroin seeking despite equal dopamine increase in self-administration and yoked groups
“inhibition of dopamine receptors in the NAcore also blocked heroin- and cue-induced drug 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.
To determine whether glutamate release in the nucleus accumbens core is necessary for heroin-induced reinstatement of drug seeking after extinction from heroin self-administration
Objective
To determine whether glutamate release in the nucleus accumbens core is necessary for heroin-induced reinstatement of drug seeking after extinction from heroin self-administration
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 paperAnimals were trained in heroin self-administration, then extinction training, then tested for reinstatement
Heroin self-administration training (2 weeks)
Extinction training (2 weeks)
Heroin-induced reinstatement testing (Not explicitly stated)
Cue-induced reinstatement testing (Not explicitly stated)
Extracellular glutamate levels in nucleus accumbens core measured by microdialysis
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
Extracellular dopamine levels in nucleus accumbens core measured by microdialysis
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
Heroin seeking behavior during reinstatement testing
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
Effects of tetrodotoxin on glutamate increase and heroin 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
Extracellular glutamate levels in nucleus accumbens core 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
Extracellular dopamine levels in nucleus accumbens core 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
Heroin seeking behavior during reinstatement testing
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
Effects of tetrodotoxin on glutamate increase and heroin 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: Extracellular glutamate levels in nucleus accumbens core measured by microdialysis; Extracellular dopamine levels in nucleus accumbens core measured by microdialysis; Heroin seeking behavior during reinstatement testing; Effects of tetrodotoxin on glutamate increase and heroin seeking.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Extracellular glutamate levels in nucleus accumbens core measured by microdialysis, Extracellular dopamine levels in nucleus accumbens core measured by microdialysis, Heroin seeking behavior during reinstatement testing, Effects of tetrodotoxin on glutamate increase and heroin seeking.
Source links and direct wording from the methods section for validation and deeper review.
Citation
Ryan T. LaLumiere et al. (2008). Glutamate Release in the Nucleus Accumbens Core Is Necessary for Heroin Seeking. Journal of Neuroscience
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What still needs work
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