Morphine reduces the interest for natural rewards.

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.