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Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaineāassociated memories in mice
- Source :
- Addiction Biology. 25
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- In drug addiction, environmental stimuli previously associated with cocaine use readily elicit cocaine-associated memories, which persist long after abstinence and trigger cocaine craving and consumption. Although previous studies suggest that the medial prefrontal cortex (mPFC) is involved in the expression of cocaine-addictive behaviors, it remains unclear whether excitatory and inhibitory neurons in the mPFC are causally related to the formation and retrieval of cocaine-associated memories. To address this issue, we used the designer receptors exclusively activated by designer drugs (DREADD) technology combined with a cocaine-induced conditioned place preference (CPP) paradigm. We suppressed mPFC neuronal activity in a cell-type- and timing-dependent manner. C57BL/6J wild-type mice received bilateral intra-mPFC infusion of an adeno-associated virus (AAV) expressing inhibitory DREADD (hM4Di) under the control of CaMKII promotor to selectively suppress mPFC pyramidal neurons. GAD67-Cre mice received bilateral intra-mPFC infusion of a Cre-dependent AAV expressing hM4Di to specifically silence GABAergic neurons. Chemogenetic suppression of mPFC pyramidal neurons significantly attenuated both the acquisition and expression of cocaine CPP, while suppression of mPFC GABAergic neurons affected neither the acquisition nor expression of cocaine CPP. Moreover, chemogenetic inhibition of mPFC glutamatergic neurons did not affect the acquisition and expression of lithium chloride-induced conditioned place aversion. These results suggest that the activation of glutamatergic, but not GABAergic, neurons in the mPFC mediates both the formation and retrieval of cocaine-associated memories.
- Subjects :
- Male
Fluorescent Antibody Technique
Prefrontal Cortex
Medicine (miscellaneous)
Biology
Inhibitory postsynaptic potential
behavioral disciplines and activities
Cocaine-Related Disorders
Mice
03 medical and health sciences
Glutamatergic
0302 clinical medicine
Cocaine
Dopamine Uptake Inhibitors
Memory
Ca2+/calmodulin-dependent protein kinase
Animals
Premovement neuronal activity
GABAergic Neurons
Prefrontal cortex
Pharmacology
musculoskeletal, neural, and ocular physiology
Conditioned place preference
030227 psychiatry
Electrophysiology
Mice, Inbred C57BL
Disease Models, Animal
Psychiatry and Mental health
nervous system
Excitatory postsynaptic potential
GABAergic
Neuroscience
psychological phenomena and processes
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 13691600 and 13556215
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Addiction Biology
- Accession number :
- edsair.doi.dedup.....06df8882011f829e01f8d60d136b1e07