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Separate vmPFC Ensembles Control Cocaine Self-Administration Versus Extinction in Rats
- Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience. 39(37)
- Publication Year :
- 2019
-
Abstract
- Recent studies suggest that the ventral medial prefrontal cortex (vmPFC) encodes both operant drug self-administration and extinction memories. Here, we examined whether these opposing memories are encoded by distinct neuronal ensembles within the vmPFC with different outputs to the nucleus accumbens (NAc) in male and female rats. Using cocaine self-administration (3 h/d for 14 d) and extinction procedures, we demonstrated that vmPFC was similarly activated (indexed by Fos) during cocaine-seeking tests after 0 (no-extinction) or 7 extinction sessions. Selective Daun02 lesioning of the self-administration ensemble (no-extinction) decreased cocaine seeking, whereas Daun02 lesioning of the extinction ensemble increased cocaine seeking. Retrograde tracing with fluorescent cholera toxin subunit B injected into NAc combined with Fos colabeling in vmPFC indicated that vmPFC self-administration ensembles project to NAc core while extinction ensembles project to NAc shell. Functional disconnection experiments (Daun02 lesioning of vmPFC and acute dopamine D1-receptor blockade with SCH39166 in NAc core or shell) confirm that vmPFC ensembles interact with NAc core versus shell to play dissociable roles in cocaine self-administration versus extinction, respectively. Our results demonstrate that neuronal ensembles mediating cocaine self-administration and extinction comingle in vmPFC but have distinct outputs to the NAc core and shell that promote or inhibit cocaine seeking. SIGNIFICANCE STATEMENT Neuronal ensembles within the vmPFC have recently been shown to play a role in self-administration and extinction of food seeking. Here, we used the Daun02 chemogenetic inactivation procedure, which allows selective inhibition of neuronal ensembles identified by the activity marker Fos, to demonstrate that different ensembles for cocaine self-administration and extinction memories coexist in the ventral mPFC and interact with distinct subregions of the nucleus accumbens.
- Subjects :
- 0301 basic medicine
Male
Infralimbic cortex
Drug-Seeking Behavior
Prefrontal Cortex
Self Administration
Nucleus accumbens
Selective inhibition
medicine.disease_cause
Nucleus Accumbens
Extinction, Psychological
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Cocaine
Dopamine Uptake Inhibitors
Dopamine
medicine
Animals
Rats, Long-Evans
Research Articles
Chemistry
General Neuroscience
Cholera toxin
social sciences
medicine.disease
Retrograde tracing
humanities
Rats
030104 developmental biology
medicine.anatomical_structure
Extinction (neurology)
Conditioning, Operant
Nerve Net
Rats, Transgenic
Self-administration
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 15292401
- Volume :
- 39
- Issue :
- 37
- Database :
- OpenAIRE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Accession number :
- edsair.doi.dedup.....78f75d2912b7a205e9a77389cbcfdf0b