The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue.

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Our findings suggest that calcium mediated toxicity is primary to the cause and progression of Parkinsonism and targeting receptors that primarily modulates calcium reduces the morphological and behavioral deficits in drug induced Parkinsonism. VDR activation was more effective than NMDAR inhibition and a combined intervention. We conclude that targeting VDR is key for controlling calcium toxicity in drug/chemotoxin induced Parkinsonism.

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Objectives Hyperinsulinemia increases the risk factor of diabetes and infertility at a manifold. Lactobacillus plantarum has several medical significances with limited reports. Hence, this study assessed the effect of L. plantarum on sexual-reproductive functions and distribution of insulin receptors in the hypothalamic-pituitary-testicular axis of hyperinsulinemic mice. Methods Forty male adult mice were divided into five groups as follows: control, high-fat diet (HFD) + streptozotocin (STZ), therapeutic, co-administration group type 1 (CO-AD) and probiotics. They were either simultaneously exposed to an HFD and L. plantarum treatment for 28 days with a dose of STZ injection to induce hyperinsulinemia on day 28 or treated with L. plantarum for 14 days, and following induction of hyperinsulinemia. Mice were subjected to a sexual behavioural test and thereafter sacrificed under euthanasia condition. Blood, brain and testes were collected for biochemical and immunohistochemical assays. Results Treatment with L. plantarum ameliorated reproductive hormones activity disruption, sexual behavioural defects, antioxidant imbalance, insulin dysregulation and lipid metabolism dysfunction following exposure to HFD + STZ when compared to the hyperinsulinemic untreated mice. Conclusions Taken together, data from this study reveal that L. plantarum abrogated hyperinsulinemia-induced male sexual and reproductive deficits by modulating antioxidant status, lipid metabolism and insulin signalling in the hypothalamic-pituitary-testicular axis of mice.

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