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Background Caffeine is a natural alkaloid present in a variety of highly consumed popular drinks such as coffee, tea and soft drinks as well as chocolate. Its consumption elicits beneficiary psychostimulant that has been linked to a reduced risk of developing Parkinson’s disease (PD). The aim of the present study is to investigate the possible synergistic neuroprotective effects of co-administration of caffeine (CAF) or coffee (COF) with rasagiline (R) or  l -dopa against paraquat (PQ)-induced neurochemical and motor behavior impairments in mice. Results In behavioral tests, R + COF increased the locomotor activity in rotarod test compared to  l -dopa + COF.  l -Dopa combinations decreased the immobility time in FST compared to rasagiline combinations;  l -dopa + CAF provided a similar increase in locomotor activity compared to R + CAF. Combination of CAF or COF with  l -dopa or rasagiline resulted in a substantial improvement in brain neurotransmitter and antioxidant levels as they significantly increased dopamine and super oxide dismutase but significantly decreased nitric oxide levels as compared to  l -dopa or rasagiline, respectively. Furthermore, they also exerted a protective effect against the neurodegenerative histopathological changes induced by PQ. Conclusions Our findings demonstrated co-administration of COF or CAF, adenosine 2A receptor antagonists, along with  l -dopa or rasagiline possesses a new therapeutic strategy for the management of PD neurochemical disturbances and motor behavior impairments through preservation of the brain dopamine and serotonin content, antioxidants level and histological features.

Simultaneous administration of coffee and rasagiline/l-dopa protects against paraquat-induced neurochemical and motor behavior impairments in vivo