Exposure to mephedrone during gestation increases the risk of stillbirth and induces hippocampal neurotoxicity in mice offspring

Abstract

In recent years, abuse of synthetic cathinones, in particular, mephedrone, has increased among young adults worldwide. The study aim is to investigate the effects of mephedrone exposure during the gestational period on mice offspring outcomes, focusing on hippocampal neurotoxicity. The pregnant mice received mephedrone (50 mg/kg, sc) on a regular schedule (once daily on all days, from day 5 to 18 of gestation) or repeated schedule (thrice daily on day 5, 6, 11, 12, 17, and 18 of gestation) to simulate regular or recreational use of mephedrone, respectively. Results showed that the percentage of weight gain in pregnant mice was significantly lower in both regular and repeated schedule mephedrone groups (p < 0.01). Also, mephedrone significantly reduced the number and weight of delivered pups and increased the rate of stillbirth (p < 0.05). Immunohistochemistry and TUNEL assay showed an inhibition of cell proliferation (p < 0.05) and an increase of apoptosis (p < 0.05) in the hippocampus of delivered pups of the repeated schedule mephedrone group. This apoptotic effect was associated with enhanced expression of the pro-apoptotic Bax gene (p < 0.05) and reduction of expression of the anti-apoptotic Bcl-2 gene (p < 0.05) as evaluated by real-time PCR. The Morris water maze showed an impairment of spatial learning (p < 0.05) and reference memory (p < 0.01) in offspring born from litters exposed to mephedrone (repeated schedule). In conclusion, the present study has shown that regular and repeated exposure to mephedrone during the gestational period increases the risk of low birth weight and stillbirth. Also, repeated use of mephedrone impairs learning and memory processes through hippocampal damage.