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Stress-induced activation of ventral tegmental mu-opioid receptors reduces accumbens dopamine tone by enhancing dopamine transmission in the medial pre-frontal cortex

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Abstract

Rationale

Endogenous opioids could play a major role in the mesocorticolimbic dopamine (DA) responses to stress challenge. However, there is still no direct evidence of an influence of endogenous opioids on any of these responses.

Objective

We assessed whether and how endogenous opioids modulate fluctuations of mesocortical and mesoaccumbens DA tone in rats during a first experience with restraint stress.

Method

We first evaluated the effects of systemic naltrexone (NTRX) on DA outflow in the medial prefrontal cortex (mpFC) and in the nucleus accumbens (NAc) through dual-probe microdialysis. Second, we assessed the effect of perfusion, through reverse microdialysis, of direct DA receptor agonists in mpFC on NAc DA outflow in NTRX-pretreated stressed rats. Finally, we tested the effects of ventral tegmental area (VTA) perfusion of NTRX, the selective mu1 antagonist naloxonazine and the selective delta antagonist naltrindole on mpFC and NAc DA outflow in stressed rats, with multiple probe experiments.

Results

Systemic NTRX, at behaviorally effective doses, selectively prevented the increase of mpFC DA levels and the reduction of NAc DA levels observable during prolonged restraint. Local co-perfusion of D1 and D2 agonists in mpFC recovered inhibition of NAc DA in NTRX-pretreated restrained rats. Finally, intra-VTA perfusion of either NTRX or the mu1 antagonist, but not the delta antagonist, mimicked the effects of systemic NTRX.

Conclusion

During prolonged experience with a novel unavoidable/uncontrollable stressor, endogenous opioids, through stimulation of mu1 receptors in the VTA, elevate mesocortical DA tone thus reducing DA tone in the NAc DA.

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Acknowledgements

We thank Dr. Sergio Papalia for his skillful assistance. This work was supported by “Ricerca Corrente”, Italian Ministry of Health and Ateneo 2011, Sapienza University of Rome.

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Authors and Affiliations

  1. Dipartimento di Psicologia e Centro “Daniel Bovet”, Sapienza University, via dei Marsi 78, 00185, Rome, Italy

    Emanuele Claudio Latagliata, Alessandro Valzania, Tiziana Pascucci, Paolo Campus, Simona Cabib & Stefano Puglisi-Allegra

  2. Fondazione Santa Lucia, IRCCS, via del Fosso di Fiorano 65, 00143, Rome, Italy

    Emanuele Claudio Latagliata, Alessandro Valzania, Tiziana Pascucci, Paolo Campus, Simona Cabib & Stefano Puglisi-Allegra

Authors
  1. Emanuele Claudio Latagliata
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  2. Alessandro Valzania
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  3. Tiziana Pascucci
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  4. Paolo Campus
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  5. Simona Cabib
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  6. Stefano Puglisi-Allegra
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Correspondence to Emanuele Claudio Latagliata.

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Latagliata, E.C., Valzania, A., Pascucci, T. et al. Stress-induced activation of ventral tegmental mu-opioid receptors reduces accumbens dopamine tone by enhancing dopamine transmission in the medial pre-frontal cortex. Psychopharmacology 231, 4099–4108 (2014). https://doi.org/10.1007/s00213-014-3549-7

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  • DOI: https://doi.org/10.1007/s00213-014-3549-7

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