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

•Increased AMPA/NMDA is key in mesolimbic cocaine-evoked sequential plasticity.•aPKCs mediate cocaine-evoked synaptic potentiation in the VTA.•Disruption of aPKC-mediated increase AMPA/NMDA decrease cocaine-evoked behavior. Chronic cocaine exposure produces enduring neuroadaptations in the brain’s r...

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Bibliographic Details
Published in:Neuroscience 2018-11, Vol.392, p.129-140
Main Authors: Vaquer-Alicea, Ana del C., Vázquez-Torres, Rafael, Devarie-Hornedo, Marcos, Vicenty-Padilla, Juan C., Santos-Vera, Bermary, María-Ríos, Cristina, Vélez-Hernández, Maria E., Sacktor, Todd, Jiménez-Rivera, Carlos A.
Format: Article
Language:English
Subjects:
NAc plasticity
PKM-ζ
Sprague Dawley
VTA plasticity
ZIP
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Summary:•Increased AMPA/NMDA is key in mesolimbic cocaine-evoked sequential plasticity.•aPKCs mediate cocaine-evoked synaptic potentiation in the VTA.•Disruption of aPKC-mediated increase AMPA/NMDA decrease cocaine-evoked behavior. 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.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2018.09.011