behavioralNot explicitly stated in provided textNot explicitly stated in provided text
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
Materials & Equipment Checklist
6 items
Gather these items before starting the experiment. Check off items as you prepare.
Equipment1
Not explicitly stated • Not explicitly stated • Not explicitly stated • Not explicitly stated
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Protocol Steps
View Abstract
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.
1
Heroin self-administration training
Animals were trained to self-administer heroin
2 weeksNot explicitly stated
Note: Initial training phase before extinction
View evidence from paper
“After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training”
2
Extinction training
Animals underwent extinction training to reduce heroin seeking after self-administration training
2 weeksNot explicitly stated
Note: Conducted after heroin self-administration training
View evidence from paper
“After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training”
3
Heroin-induced reinstatement testing
Heroin seeking was induced by a noncontingent injection of heroin in animals previously extinguished from heroin self-administration
Not explicitly statedNot explicitly stated
Note: Microdialysis conducted during this phase to measure glutamate changes
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”
4
Cue-induced reinstatement testing
Heroin seeking was induced by presentation of light and tone cues previously paired with heroin infusions
Not explicitly statedNot explicitly stated
Note: Conducted in parallel with heroin-induced reinstatement testing
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”
5
Yoked control group testing
Parallel groups received noncontingent saline or heroin injections while undergoing microdialysis
Not explicitly statedNot explicitly stated
Note: Control groups to compare glutamate responses between self-administration trained and yoked animals
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”
6
Tetrodotoxin inhibition testing
Synaptic transmission in the nucleus accumbens core was inhibited with tetrodotoxin during heroin-induced reinstatement
Not explicitly statedNot explicitly stated
Note: To test whether synaptic transmission is necessary for glutamate increase during heroin seeking
View evidence from paper
“increase in glutamate during heroin-induced drug seeking was abolished by inhibiting synaptic transmission in the NAcore with tetrodotoxin”