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Morphine reduces the interest for natural rewards

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Abstract

Rationale

Alongside a pathological, excessive, motivation for substances of abuse, substance use disorder (SUD) patients often show a dramatic loss of interest for naturally rewarding activities, such as positive peer social interaction and food intake. Yet, pre-clinical evidence of the latter SUD features remains scarce and inconsistent.

Objectives

In the current study, we investigated the effect of non-rewarding and rewarding doses of morphine upon social behaviour, motivation for and intake of palatable food, in male and female C57BL/6J mice.

Methods

First, the rewarding effects of two relatively low morphine doses (1.25 and 2.5 mg/kg) were assessed using a newly established single substance administration/conditioning trial conditioned place preference (CPP) paradigm. Then, morphine (1.25 and 2.5 mg/kg) effects upon social behaviour, motivation for and intake of palatable food were examined by the three-chamber (3-CH), an operant behaviour and a palatable food preference test, respectively.

Results

Morphine (2.5 mg/kg) induced CPP in both male and female mice, whereas morphine (1.25 mg/kg) induced CPP only in female mice. Both morphine doses (1.25 and 2.5 mg/kg) reduced sociability, motivation for and intake of palatable food in male and female mice, independently of cognitive function or locomotor activity.

Conclusions

Female mice were more sensitive than male mice to the rewarding effects of morphine. Moreover, both a non-rewarding and a rewarding dose of morphine impaired the interest for naturally rewarding activities, indicating that brain reward systems might be more sensitive to the deleterious than to the rewarding effects of substances of abuse.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by the Fondation pour la Recherche Médicale (FRM grant n. DPA20140629794 to AC), the University of Bordeaux and the Centre National de la Recherche Scientifique (CNRS), France. Funding sources had no further role in study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the paper for publication.

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All authors had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. Conceptualization: A.P. and A.C. Methodology: A.P., G.C. and A.C. Investigation: A.P. Formal analysis: A.P., G.C. and A.C. Resources: A.C. Writing: A.P and A.C. Supervision: A.C. Funding acquisition: A.C.

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Correspondence to Angelo Contarino.

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Piccin, A., Courtand, G. & Contarino, A. Morphine reduces the interest for natural rewards. Psychopharmacology 239, 2407–2419 (2022). https://doi.org/10.1007/s00213-022-06131-7

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