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Effects of morphine on place conditioning and ERK1/2 phosphorylation in the nucleus accumbens of psychogenetically selected Roman low- and high-avoidance rats

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Abstract

Rationale

Extracellular signal-regulated kinase (ERK1/2) phosphorylation is critical for neuronal and behavioural functions; in particular, phosphorylated ERK1/2 (pERK1/2) expression in the nucleus accumbens (Acb) of the rat is stimulated by addictive drugs with the exception of morphine, which decreases accumbal ERK1/2 phosphorylation in the Sprague-Dawley and Wistar rats. The psychogenetically selected Roman low- (RLA) and high-avoidance (RHA) rats differ behaviourally and neurochemically in many responses to addictive drugs. In particular, morphine elicits a greater increment in locomotor activity and in dopamine transmission in the Acb of RHA vs RLA rats. However, the effects of morphine on place conditioning (conditioned place preference (CPP)) and ERK1/2 phosphorylation in the Roman lines remain unknown.

Objectives and methods

To characterize in the Roman lines the reinforcing properties of morphine (i.e. morphine-elicited CPP acquisition) and the relationship between these properties and its effects on ERK1/2 phosphorylation in the Acb, the behavioural effects of morphine were evaluated in a place-conditioning apparatus and ERK1/2 phosphorylation was assessed by immunohistochemistry in the shell and core subregions of the Acb of rats both acutely administered with morphine or undergoing conditioning.

Results

Morphine elicited CPP in both Roman lines and decreased pERK1/2 expression in the Acb of RLA but not RHA rats. Such decrease was prevented by conditioning.

Conclusions

These findings indicate that the selective breeding of the Roman lines has generated a divergence, in terms of morphine-elicited pERK1/2 expression but not of morphine-elicited CPP, between RLA and RHA rats and sustain the observation that changes in pERK1/2 expression in the Acb are not a requisite for the reinforcing effects of morphine.

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Funding

This study was supported by funds from MIUR (Ministero dell’Istruzione, Università e Ricerca, PRIN), Regione Autonoma della Sardegna (RAS) (L.R. 7/2007, CRP2_537), Fondazione Banco di Sardegna (Sassari, Italy) and from the University of Cagliari to EA and by grants from MIUR to OG and MGC and from RAS (L.R. 7/2007, CRP-59842) to OG.

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Authors and Affiliations

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

    Michela Rosas, Simona Porru, Maria Antonietta Piludu, Osvaldo Giorgi, Maria G. Corda & Elio Acquas

  2. Neurobiology Section and Center for Neural Circuits and Behavior, Division of Biological Sciences, University of California, San Diego, USA

    Marta Sabariego

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

    Elio Acquas

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  1. Michela Rosas
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  2. Simona Porru
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  3. Marta Sabariego
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  4. Maria Antonietta Piludu
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  5. Osvaldo Giorgi
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  6. Maria G. Corda
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  7. Elio Acquas
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Correspondence to Elio Acquas.

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Rosas, M., Porru, S., Sabariego, M. et al. Effects of morphine on place conditioning and ERK1/2 phosphorylation in the nucleus accumbens of psychogenetically selected Roman low- and high-avoidance rats. Psychopharmacology 235, 59–69 (2018). https://doi.org/10.1007/s00213-017-4740-4

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  • DOI: https://doi.org/10.1007/s00213-017-4740-4

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