| First Author | Hearing M | Year | 2013 |
| Journal | Neuron | Volume | 80 |
| Issue | 1 | Pages | 159-70 |
| PubMed ID | 24094109 | Mgi Jnum | J:248661 |
| Mgi Id | MGI:6093911 | Doi | 10.1016/j.neuron.2013.07.019 |
| Citation | Hearing M, et al. (2013) Repeated cocaine weakens GABA(B)-Girk signaling in layer 5/6 pyramidal neurons in the prelimbic cortex. Neuron 80(1):159-70 |
| abstractText | 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/K(IR)3 channels mediate most of the GABA(B) receptor (GABA(B)R)-dependent inhibition of layer 5/6 pyramidal neurons in the mPFC and that repeated cocaine suppresses this pathway. This adaptation was selective for GABA(B)R-dependent Girk signaling in layer 5/6 pyramidal neurons of the prelimbic cortex (PrLC) and involved a D(1)/(5) dopamine receptor- and phosphorylation-dependent internalization of GABA(B)R and Girk channels. Persistent suppression of Girk signaling in layer 5/6 of the dorsal mPFC enhanced cocaine-induced locomotor activity and occluded behavioral sensitization. Thus, the cocaine-induced suppression of GABA(B)R-Girk signaling in layer 5/6 pyramidal neurons of the prelimbic cortex appears to represent an early adaptation critical for promoting addiction-related behavior. |
