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Role of nucleus accumbens μ opioid receptors in the effects of morphine on ERK1/2 phosphorylation

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Abstract

Rationale

Despite the critical role attributed to phosphorylated extracellular signal regulated kinase (pERK1/2) in the nucleus accumbens (Acb) in the actions of addictive drugs, the effects of morphine on ERK1/2 phosphorylation in this area are still controversial.

Objectives

In order to investigate further this issue, we studied (1) the ability of morphine to affect ERK1/2 phosphorylation in the shell (AcbSh) and core (AcbC) of Sprague-Dawley and Wistar rats and of CD-1 and C57BL/6J mice and (2) the role of dopamine D1 and μ-opioid receptors in Sprague-Dawley rats and CD-1 mice.

Methods

The pERK1/2 expression was assessed by immunohistochemistry.

Results

In rats, morphine decreased AcbSh and AcbC pERK1/2 expression, whereas in mice, increased it preferentially in the AcbSh compared with the AcbC. Systemic SCH 39166 decreased pERK1/2 expression on its own in the AcbSh and AcbC of Sprague-Dawley rats and CD-1 mice; furthermore, in rats, SCH 39166 disclosed the ability of morphine to stimulate pERK1/2 expression. Systemic (rats and mice) and intra-Acb (rats) naltrexone prevented both decreases, in rats, and increases, in mice.

Conclusions

These findings confirm the differential effects of morphine in rats and mice Acb and that D1 receptors exert a facilitatory role on ERK1/2 phosphorylation; furthermore, they indicate that, in rats, removal of the D1-dependent pERK1/2 expression discloses the stimulatory influence of morphine on ERK1/2 phosphorylation and that the morphine’s ability to decrease pERK1/2 expression is mediated by Acb μ-opioid receptors. Future experiments may disentangle the psychopharmacological significance of the effects of morphine on pERK1/2 in the Acb.

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This study was supported by funds from Ministero dell’Istruzione, Università e Ricerca, PRIN (MIUR), Regione Autonoma della Sardegna (RAS), Fondazione Banco di Sardegna (Sassari, Italy), and from the University of Cagliari to E. Acquas.

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Authors and Affiliations

  1. Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale, 72, I-09124, Cagliari, Italy

    Michela Rosas, Simona Porru & Elio Acquas

  2. Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy

    Sandro Fenu & Gaetano Di Chiara

  3. Institute of Translational Pharmacology, National Research Council, Pula, Cagliari, Italy

    Stefania Ruiu

  4. Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy

    Alessandra T. Peana

  5. Neuroscience and Mental Health Research Institute (NMHRI), Neuroscience Division - School of Biosciences, Cardiff University, Cardiff, UK

    Alessandro Papale & Riccardo Brambilla

  6. Centre of Excellence on Neurobiology of Addiction, University of Cagliari, Cagliari, Italy

    Sandro Fenu, Gaetano Di Chiara & Elio Acquas

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  1. Michela Rosas
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  2. Simona Porru
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Correspondence to Elio Acquas.

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Rosas, M., Porru, S., Fenu, S. et al. Role of nucleus accumbens μ opioid receptors in the effects of morphine on ERK1/2 phosphorylation. Psychopharmacology 233, 2943–2954 (2016). https://doi.org/10.1007/s00213-016-4340-8

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