Access to high-fat diet results in increased sensitivity to the psychostimulant effects of MDPV in mice.

Background: The current study investigated the effects of high-fat diet on acute response to 3,4-methylenedioxypyrovalerone (MDPV) in mice. MDPV is a beta-cathinone derivative endowed with psychostimulant activity. Similarly to recreational substances, consumption of palatable food stimulates the mesolimbic dopaminergic system, resulting in neuroadaptive changes.

Methods: Adolescent C57BL/6N mice were fed either control diet (CD), 10% of kcal from fat, or high-fat diet (HFD), 60% of kcal from fat. After eight weeks, one group of HFD-fed mice had their diet changed to CD for an additional two weeks. Fasting glucose levels and glucose tolerance were measured to detect impairment in glucose metabolism. Subsequently, the mice were treated with either MDPV (1 mg/kg) or saline, and their locomotor activity was measured. Using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), the expression of dopamine receptor D1 (Drd1), dopamine receptor D2 (Drd2), and FBJ osteosarcoma oncogene B (FosB) genes was measured in the striatum of mice.

Results: Feeding with HFD caused obesity and glucose intolerance in mice. Restriction of fat reduced body mass and reversed impairment of glucose metabolism. HFD-fed mice responded to MDPV with higher potency than CD-fed counterparts, with an increased incidence of stereotypies. A change of diet partially reversed this effect. Downregulation of Drd2 was observed in the mice that switched from HFD to CD, whereas treatment with MDPV caused upregulation of FosB only in the CD-fed mice.

Conclusions: Current results suggest that obesity may increase sensitivity to psychostimulant effects of MDPV and elevate the risk of addiction as mice fed with HFD responded to acute treatment with MDPV with higher potency and showed tolerance of FosB induction in response to the drug.