Repeated Cocaine Weakens GABAB-Girk Signaling in Layer 5/6 Pyramidal Neurons in the Prelimbic Cortex

Matthew Hearing, Lydia Kotecki, Ezequiel MarronFernandezdeVelasco, Ana Fajardo-Serrano, Hee Jung Chung, Rafael Luján, Kevin Wickman

Research output: Contribution to journalArticle

Abstract

Repeated cocaine exposure triggers adaptations in layer 5/6 glutamatergic neurons in the medial prefrontal cortex (mPFC) that promote behavioral sensitization and drug-seeking behavior. While suppression of metabotropic inhibitory signaling has been implicated in these behaviors, underlying mechanisms are unknown. Here, we show that Girk/KIR3 channels mediate most of the GABAB receptor (GABABR)-dependent inhibition of layer 5/6 pyramidal neurons in the mPFC and that repeated cocaine suppresses this pathway. This adaptation was selective for GABABR-dependent Girk signaling in layer 5/6 pyramidal neurons of the prelimbic cortex (PrLC) and involved a D1/5 dopamine receptor- and phosphorylation-dependent internalization of GABABR and Girk channels. Persistent suppressionof Girk signaling in layer 5/6 of the dorsal mPFCenhanced cocaine-induced locomotor activity andoccluded behavioral sensitization. Thus, thecocaine-induced suppression of GABABR-Girk signaling in layer 5/6 pyramidal neurons of the prelimbic cortex appears to represent an early adaptation critical for promoting addiction-related behavior

Original languageEnglish (US)
Pages (from-to)159-170
Number of pages12
JournalNeuron
Volume80
Issue number1
DOIs
StatePublished - Oct 2 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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    Hearing, M., Kotecki, L., MarronFernandezdeVelasco, E., Fajardo-Serrano, A., Chung, H. J., Luján, R., & Wickman, K. (2013). Repeated Cocaine Weakens GABAB-Girk Signaling in Layer 5/6 Pyramidal Neurons in the Prelimbic Cortex. Neuron, 80(1), 159-170. https://doi.org/10.1016/j.neuron.2013.07.019