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 seeking induced by cue presentation or heroin priming after extinction of heroin self-administration
This is a Cue-Induced Reinstatement protocol using rat as the model organism. The procedure involves 9 procedural steps, 3 equipment items, 5 materials. Extracted from a 2008 paper published in Journal of Neuroscience.
Model and subjects
rat • Not specified • unknown • Not specified • Not specified
Study window
~2 week study window
Core workflow
Heroin self-administration training • Extinction training • Cue-induced reinstatement testing
Primary readouts
Key equipment and reagents
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Animals were trained to self-administer heroin for 2 weeks
Note: Self-administration group only
“After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training”
Animals underwent extinction training where heroin was no longer available following the self-administration period
Note: Self-administration group only
“After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training”
Heroin seeking was induced by presentation of light and tone cues that were previously paired with heroin infusions during self-administration
Note: Conducted in self-administration group and yoked control groups
“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 a noncontingent injection of heroin
Note: Conducted in self-administration group and yoked control groups
“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 nucleus accumbens core to measure extracellular glutamate during reinstatement testing
Note: Conducted simultaneously with reinstatement testing
“Microdialysis was conducted in the NAcore during reinstatement of heroin seeking in animals extinguished from heroin self-administration”
Synaptic transmission in the nucleus accumbens core was inhibited with tetrodotoxin to test its effect on glutamate increase during heroin-induced drug seeking
Note: Tetrodotoxin abolished the increase in glutamate during heroin-induced drug seeking
“The 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 to test their necessity for heroin-induced drug seeking
Note: Inhibition of these afferents abolished the increase in glutamate during heroin-induced drug seeking
“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”
AMPA/kainate glutamate receptors in the nucleus accumbens core were inhibited to test their role in heroin and cue-induced drug seeking
Note: Inhibition of these receptors blocked both heroin-induced and cue-induced 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 to test their role in heroin and cue-induced drug seeking
Note: Inhibition of dopamine receptors blocked both heroin-induced and cue-induced heroin seeking despite equal dopamine increase in both self-administration and yoked-saline 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 seeking induced by cue presentation or heroin priming after extinction of heroin self-administration
Objective
To determine whether glutamate release in the nucleus accumbens core is necessary for heroin seeking induced by cue presentation or heroin priming after extinction of heroin self-administration
Subjects
From paperrat • Not specified • unknown • Not specified • Not specified
Cohort notes
From paperAnimals were divided into self-administration group, yoked-saline control group, and yoked-heroin control group
Heroin self-administration training (2 weeks)
Extinction training (2 weeks)
Cue-induced reinstatement testing (Not specified)
Heroin-induced reinstatement testing (Not specified)
Extracellular glutamate levels in the nucleus accumbens core during reinstatement
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
Extracellular dopamine levels in the nucleus accumbens core during reinstatement
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
Heroin seeking behavior induced by light/tone cues
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
Heroin seeking behavior induced by heroin priming injection
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
Extracellular glutamate levels in the nucleus accumbens core during reinstatement
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 the nucleus accumbens core during reinstatement
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 induced by light/tone cues
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 induced by heroin priming injection
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: Extracellular glutamate levels in the nucleus accumbens core during reinstatement; Extracellular dopamine levels in the nucleus accumbens core during reinstatement; Heroin seeking behavior induced by light/tone cues; Heroin seeking behavior induced by heroin priming injection.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Extracellular glutamate levels in the nucleus accumbens core during reinstatement, Extracellular dopamine levels in the nucleus accumbens core during reinstatement, Heroin seeking behavior induced by light/tone cues, Heroin seeking behavior induced by heroin priming injection.
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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