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: | Maria E. Velez-Hernandez, Marcos Devarie-Hornedo, Carlos A. Jiménez-Rivera, Bermary Santos-Vera, Ana del C. Vaquer-Alicea, Cristina María-Ríos, Todd Charlton Sacktor, Rafael Vázquez-Torres, Juan C. Vicenty-Padilla |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chemistry General Neuroscience musculoskeletal neural and ocular physiology Long-term potentiation AMPA receptor Nucleus accumbens Article Ventral tegmental area 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure nervous system Synaptic plasticity Neuroplasticity medicine NMDA receptor Neuroscience 030217 neurology & neurosurgery Sensitization |
| Popis: | Chronic cocaine exposure produces enduring neuroadaptations in the brain’s reward system. Persistence of early cocaine evoked neuroadaptations in the ventral tegmental area (VTA) are 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 aPKC’s, could be the molecular signal that enables the VTA to elicit synaptic alterations in the NAc following cocaine administration. |
| Databáze: | OpenAIRE |
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