Journal article
Glutamate release in the nucleus accumbens core is necessary for heroin seeking
The Journal of neuroscience, Vol.28(12), pp.3170-3177
03/19/2008
DOI: 10.1523/JNEUROSCI.5129-07.2008
PMCID: PMC6670700
PMID: 18354020
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.
Details
- Title: Subtitle
- Glutamate release in the nucleus accumbens core is necessary for heroin seeking
- Creators
- Ryan T LaLumiere - Neurobiology of Addiction Research Center, Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA. lalumie@musc.eduPeter W Kalivas
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.28(12), pp.3170-3177
- Publisher
- United States
- DOI
- 10.1523/JNEUROSCI.5129-07.2008
- PMID
- 18354020
- PMCID
- PMC6670700
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- DA 021460 / NIDA NIH HHS 015369 / PHS HHS
- Language
- English
- Date published
- 03/19/2008
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9984070668602771
Metrics
9 Record Views