Caffeine and nicotine in a Parkinson’s disease’s animal model: from olfactory improvement to neuroprotection

Abstract Parkinson's disease motor disorders are strongly associated with the degeneration of dopaminergic neurons and dopamine depletion in the nigrostriatal pathway. However, earlier, patients may have olfactory disorders. Studies have shown an inverse relationship between the consumption of caffeine or nicotine and the risk of developing Parkinson's disease. This study investigated whether the treatment with caffeine and/or nicotine would be able to prevent olfactory impairment in an animal model. Adult male and female Wistar rats received intraperitoneal saline, caffeine and/or nicotine for 7 consecutive days after intranigral injury and were submitted to behavioral tests. The treatment with caffeine and double treatment (caffeine + nicotine) reversed the olfactory impairment caused by rotenone, in male rats.In females, olfactory disturbance was not present.Surprisingly, there was no olfactory bulb (OB)tyrosine hydroxylase (TH) increased phosphorylation by the caffeine administration, present only in a double treatment, for males. In addition, a trend to increased TH phosphorylation of the nicotine rotenone group was observed, indicating a negative influence of dopamine on olfaction, probably due to its action on OB D2 inhibitory receptors, which may explain the olfactory impairment not reversed by nicotine. Besides, nicotine presented dopaminergic neurons restoration for both male and female in the substantia nigra, indicating a neuroprotective effect against rotenone lesion. Caffeine and nicotine presented different benefits in the rotenone model, improving the olfactory disturbance and reducing the neuronal loss within the substantia nigra. Additionally, the intranigral rotenone presented sex differences related to olfactory function, also present in a human population.