Journal article
Neural circuit competition in cocaine-seeking: Roles of the infralimbic cortex and nucleus accumbens shell
The European journal of neuroscience, Vol.35(3-4), pp.614-622
02/2012
DOI: 10.1111/j.1460-9568.2012.07991.x
PMCID: PMC3281521
PMID: 22321070
Abstract
Following cocaine self-administration and extinction training, activity in the infralimbic cortex (IL) suppresses cocaine-seeking behavior. IL inactivation induces cocaine-seeking, whereas activation suppresses cocaine-reinstated drug-seeking. We asked how the suppression of cocaine-seeking induced by IL activation integrates with the circuitry promoting reinstated cocaine-seeking. Following cocaine self-administration and extinction training, rats underwent cue-induced reinstatement. In order to activate IL projections, microinjections of PEPA, a positive allosteric modulator of AMPA receptors, were made into the IL in combination with microinjections into a variety of nuclei known to regulate cocaine-seeking. Intra-IL PEPA administration suppressed cue-induced reinstatement without affecting locomotor activity. The suppression of cocaine-seeking was reversed by activating dopamine neurons in the ventral tegmental area with microinjections of the μ-opioid receptor agonist DAMGO and partially reversed by dopamine microinjections into the prelimbic cortex or basolateral amygdala. Previous evidence suggests that the nucleus accumbens shell both promotes and suppresses cocaine-seeking. The suppression of cue-induced cocaine seeking by PEPA in the IL was reversed by intra-shell microinjections of either dopamine or the AMPA receptor antagonist CNQX, suggesting that the accumbens shell bidirectionally regulates cocaine-seeking depending on whether dopamine input is mimicked or glutamate input is inhibited. Together, these findings indicate that the IL acts “upstream” from structures promoting cocaine-seeking, including from the mesolimbic dopamine projections to the prelimbic cortex and basolateral amygdala and that the accumbens shell may be a crucial point of integration between the circuits that promote (ventral tegmental area) and inhibit (IL) reinstated cocaine-seeking.
Details
- Title: Subtitle
- Neural circuit competition in cocaine-seeking: Roles of the infralimbic cortex and nucleus accumbens shell
- Creators
- Ryan T LaLumiere - Department of Psychology, University of Iowa, Iowa City, IA 52242Kyle C Smith - Neurobiology of Addiction Research Center, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USAPeter W Kalivas - Neurobiology of Addiction Research Center, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA
- Resource Type
- Journal article
- Publication Details
- The European journal of neuroscience, Vol.35(3-4), pp.614-622
- DOI
- 10.1111/j.1460-9568.2012.07991.x
- PMID
- 22321070
- PMCID
- PMC3281521
- NLM abbreviation
- Eur J Neurosci
- ISSN
- 0953-816X
- eISSN
- 1460-9568
- Language
- English
- Date published
- 02/2012
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9984070256302771
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