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Norepinephrine in prelimbic cortex delays extinction of amphetamine-induced conditioned place preference

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Abstract

Rationale

Drug-associated cues exposure to induce extinction is a useful strategy to contrast cue-induced drug seeking. Treatments aimed at reducing motivational properties of cues are considered highly promising since they could decrease their ability to induce drug-conditioned behaviors. Norepinephrine (NE) in the medial prefrontal cortex (mPFC) is critical for attribution of motivational salience to highly salient stimuli, suggesting a major role in prelimbic (PL) mpFC to modulate the motivational properties of drug-related cues, invigorating them, and consequently, delaying extinction.

Objectives

To investigate if NE in PL fosters the maintenance of drug-seeking behavior, we assessed its role on amphetamine-induced conditioned place preference (CPP). Moreover, to affirm the specificity of NE in PL, we also assessed the role of NE in the infralimbic (IL) mPFC.

Methods

The effects of selective NE depletion in the PL or in the IL of C57BL/6J mice were assessed on the expression of amphetamine-induced CPP before and after extinction procedure.

Results

NE-depleted mice in PL extinguished preference for Amph-paired chamber long before sham animals. By contrast, IL-depleted animals maintained place preference for more than 4 weeks after the procedure of extinction, having at that moment interrupted the test.

Conclusions

Inactivation of NE in PL cortex blunts amphetamine-induced CPP, thus fostering extinction and showing to be critical for the maintenance of conditioned Amph-seeking behavior. Opposite effects of NE depletion in IL, seemingly in agreement with literature on extinction, are discussed in terms of balance of activity between PL and IL in extinction.

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Acknowledgments

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

    Pamela Saccoccio, Chiara Milia & Stefano Puglisi-Allegra

  2. Fondazione Santa Lucia, IRCCS, via del Fosso di Fiorano 64, 00143, Rome, Italy

    Emanuele Claudio Latagliata & Stefano Puglisi-Allegra

Authors
  1. Emanuele Claudio Latagliata
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  2. Pamela Saccoccio
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  3. Chiara Milia
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  4. Stefano Puglisi-Allegra
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Corresponding author

Correspondence to Emanuele Claudio Latagliata.

Ethics declarations

All experiments were carried out in accordance with Italian national law (DL 116/92 and DL 26/2014) on the use of animals for research based on the European Communities Council Directives (86/609/EEC and 2010/63/UE), and approved by the ethics committee of the Italian Ministry of Health (license/approval ID #: 10/2011-B and 42/2015-PR).

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The authors declare that they have no competing interests.

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Latagliata, E.C., Saccoccio, P., Milia, C. et al. Norepinephrine in prelimbic cortex delays extinction of amphetamine-induced conditioned place preference. Psychopharmacology 233, 973–982 (2016). https://doi.org/10.1007/s00213-015-4177-6

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  • DOI: https://doi.org/10.1007/s00213-015-4177-6

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