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Dopamine Neurotransmission in the Ventral Tegmental Area Promotes Active Forgetting of Cocaine-Associated Memory

  • Fernando Castillo Díaz
  • Micaela A. Hernandez
  • Tomas Capellá
  • Jorge H. MedinaEmail author
Article

Abstract

Dopamine (DA) neurons in the ventral tegmental area (VTA) are well-known components of the brain involved in reward-related behaviors and participate in the generation of new memories. Much attention has been focused to understand how DA neurons integrate a diversity of afferent signals with local excitatory and inhibitory influences regulated by somatodendritic release of dopamine. However, the mechanisms that actively forget rewarding information are still terra incognita. Using rodents in the conditioned place preference (CPP) behavioral task, we show that during acquisition D1-type DA receptors (D1R) in the VTA are crucial components of a neural circuit involving the hippocampus that induces active forgetting of cocaine-associated long-term memory, while VTA and nucleus accumbens (NAc) D1R are required for its formation. Inhibition of VTA D1R results in increased activation of VTA ERK1/2 and in prolonging memory storage of cocaine-place association in an ERK-dependent manner. Moreover, intra-VTA infusion of a specific D1 agonist induces forgetting of cocaine-associated consolidated memory. In contrast, D1R in the NAc shell, medial prefrontal cortex, or amygdala appear not to participate in the maintenance of cocaine-associated memory. Our present results suggest that at the moment of learning D1R-mediated neurotransmission in the VTA actively participates in at least two processes affecting the fate of appetitive memory: its consolidation involving NAc shell DA neurotransmission and its forgetting via DA activation of the hippocampus.

Keywords

Forgetting Dopamine VTA Cocaine Memory 

Notes

Acknowledgments

We thank Dr. Cynthia Katche, Ana Belén de Landeta and Magdalena Pereyra for their help with the biochemistry experiments and daily work in general.

Funding Information

This study was supported by grants from Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT, Argentina) to JHM; nos. 2013–0335 and 2016-0034; Universidad de Buenos Aires (UBACyT, Argentina) 2014–2017 and the Argentina National Research Council (Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2019_1516_Fig6_ESM.png (717 kb)
Figure S1

Histological analysis of cannulae placement. Schematic illustration of the injections sites in the intended areas. Top: VTA, hippocampus and mPFC; Bottom: NAc and BLA. Coordinates were measured from Bregma taken from the atlas of Paxinos and Watson (2005). (PNG 717 kb)

12035_2019_1516_MOESM1_ESM.tif (8.8 mb)
High Resolution Image (TIF 8982 kb)

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Authors and Affiliations

  1. 1.Instituto de Biología Celular y Neurociencias, Facultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

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