aPKC-Mediated Persistent Increase in AMPA/NMDA Ratio in the VTA Participates in the Neuroadaptive Signal Necessary to Induce NAc Synaptic Plasticity After Cocaine Administration.

Autor: Vaquer-Alicea ADC; Department of Physiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico., Vázquez-Torres R; Department of Physiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico., Devarie-Hornedo M; School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico., Vicenty-Padilla JC; Department of Neurosurgery, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico., Santos-Vera B; Department of Physiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico., María-Ríos C; Department of Biology, University of Puerto Rico Rio Piedras Campus, San Juan, Puerto Rico., Vélez-Hernández ME; Department of Biological and Health Sciences, University of Houston-Victoria, Houston, TX, USA., Sacktor T; Department of Physiology and Pharmacology, The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA., Jiménez-Rivera CA; Department of Physiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. Electronic address: carlos.jimenez8@upr.edu.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2018 Nov 10; Vol. 392, pp. 129-140. Date of Electronic Publication: 2018 Sep 21.
DOI: 10.1016/j.neuroscience.2018.09.011
Abstrakt: Chronic cocaine exposure produces enduring neuroadaptations in the brain's reward system. Persistence of early cocaine-evoked neuroadaptations in the ventral tegmental area (VTA) is necessary for later synaptic alterations in the nucleus accumbens (NAc), suggesting a temporal sequence of neuroplastic changes between these two areas. However, the molecular nature of the signal that mediates this sequential event is unknown. Here we used the behavioral sensitization model and the aPKC inhibitor of late-phase LTP maintenance, ZIP, to investigate if a persistent increase in AMPA/NMDA ratio plays a role in the molecular mechanism that allows VTA neuroadaptations to induce changes in the NAc. Results showed that intra-VTA ZIP microinfusion successfully blocked cocaine-evoked synaptic enhancement in the VTA and the expected AMPA/NMDA ratio decrease in the NAc following cocaine sensitization. ZIP microinfusions also blocked the expected AMPA/NMDA ratio increase in the NAc following cocaine withdrawal. These results suggest that a persistent increase in AMPA/NMDA ratio, mediated by aPKCs, could be the molecular signal that enables the VTA to elicit synaptic alterations in the NAc following cocaine administration.
(Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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