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Glutamatergic neurotransmission in the prefrontal cortex mediates the suppressive effect of intra-prelimbic cortical infusion of BDNF on cocaine-seeking.


ABSTRACT: Cocaine self-administration induces dysfunctional neuroadaptations in the prefrontal cortex that underlie relapse to cocaine-seeking. Cocaine self-administration disturbs glutamatergic transmission in the nucleus accumbens that is prevented by infusion of brain-derived neurotrophic factor (BDNF) into the prelimbic area of the prefrontal cortex. Intra-prelimbic infusion of BDNF decreases cocaine-seeking in a TrkB-ERK MAP kinase-dependent manner. Neuronal activity triggers an interaction between TrkB receptors and NMDA receptors, leading to ERK activation. In the present study, infusion of the GluN2A-containing NMDA receptor antagonist, TCN-201, or the GluN2B-containing NMDA receptor antagonist, Ro-25-6981, into the prelimbic cortex of rats blocked the suppressive effect of BDNF on cocaine-seeking. During early withdrawal from cocaine self-administration, tyrosine phosphorylation of ERK, GluN2A, and GluN2B in the prelimbic cortex was reduced and this reduction of phospho-proteins was prevented by intra-prelimbic BDNF infusion. TCN-201 infusion into the prelimbic cortex inhibited the BDNF-mediated increase in pERK and pGluN2A whereas Ro-25-6981 infusion into the prelimbic cortex blocked BDNF-induced elevation of pERK and pGluN2B, indicating that both GluN2A- and GluN2B-containing NMDA receptors underlie BDNF-induced ERK activation. These data demonstrate that BDNF-mediated activation of GluN2A- and GluN2B-containing NMDA receptors underlies ERK activation in the prelimbic cortex during early withdrawal, preventing subsequent relapse to cocaine-seeking.

SUBMITTER: Go BS 

PROVIDER: S-EPMC5136511 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Glutamatergic neurotransmission in the prefrontal cortex mediates the suppressive effect of intra-prelimbic cortical infusion of BDNF on cocaine-seeking.

Go Bok Soon BS   Barry Sarah M SM   McGinty Jacqueline F JF  

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 20161017 12


Cocaine self-administration induces dysfunctional neuroadaptations in the prefrontal cortex that underlie relapse to cocaine-seeking. Cocaine self-administration disturbs glutamatergic transmission in the nucleus accumbens that is prevented by infusion of brain-derived neurotrophic factor (BDNF) into the prelimbic area of the prefrontal cortex. Intra-prelimbic infusion of BDNF decreases cocaine-seeking in a TrkB-ERK MAP kinase-dependent manner. Neuronal activity triggers an interaction between T  ...[more]

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