Source Paper
Glutamate Release in the Nucleus Accumbens Core Is Necessary for Heroin Seeking
Ryan T. LaLumiere, Peter W. Kalivas
Journal of Neuroscience • 2008
Heroin Self-Administration
Objective: To determine whether glutamate release in the nucleus accumbens core is necessary for heroin seeking during reinstatement after extinction training
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Equipment2
Materials3
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Protocol Steps
Heroin Self-Administration Training
Animals were trained to self-administer heroin intravenously
Note: Training period establishing drug-seeking behavior
View evidence from paper
“After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training”
Extinction Training
Animals underwent extinction training where heroin infusions were no longer available
Note: Extinction period to reduce heroin-seeking behavior
View evidence from paper
“After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training”
Reinstatement Testing - Heroin-Induced
Heroin seeking was induced by a noncontingent injection of heroin
Note: Testing reinstatement of drug-seeking behavior
View evidence from paper
“heroin seeking was induced by a noncontingent injection of heroin or by presentation of light/tone cues previously paired with heroin infusions”
Reinstatement Testing - Cue-Induced
Heroin seeking was induced by presentation of light/tone cues previously paired with heroin infusions
Note: Testing cue-induced reinstatement of drug-seeking behavior
View evidence from paper
“heroin seeking was induced by a noncontingent injection of heroin or by presentation of light/tone cues previously paired with heroin infusions”
Microdialysis Sampling
Microdialysis was conducted in the nucleus accumbens core during reinstatement testing to measure extracellular glutamate and dopamine
Note: Conducted in self-administration group and yoked control groups receiving noncontingent saline or heroin
View evidence from paper
“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”
Tetrodotoxin Inhibition Test
Synaptic transmission in the nucleus accumbens core was inhibited with tetrodotoxin to test necessity of glutamate release
Note: Testing whether glutamate transmission is necessary for heroin-induced drug seeking
View evidence from paper
“The increase in glutamate during heroin-induced drug seeking was abolished by inhibiting synaptic transmission in the NAcore with tetrodotoxin”
Glutamatergic Afferent Inhibition Test
Glutamatergic afferents to the nucleus accumbens core from the prelimbic cortex were inhibited
Note: Testing necessity of prelimbic cortex glutamatergic projection
View evidence from paper
“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 Receptor Inhibition Test
AMPA/kainate glutamate receptors in the nucleus accumbens core were inhibited
Note: Testing whether glutamate receptor activation is necessary for heroin and cue-induced drug seeking
View evidence from paper
“heroin seeking induced by cue or heroin was blocked by inhibiting AMPA/kainate glutamate receptors in the NAcore”
Dopamine Receptor Inhibition Test
Dopamine receptors in the nucleus accumbens core were inhibited
Note: Testing role of dopamine in heroin and cue-induced drug seeking
View evidence from paper
“inhibition of dopamine receptors in the NAcore also blocked heroin- and cue-induced drug seeking”