Caffeine plus haloperidol reduces fatigue in an experimental model of Parkinson's disease - a prospective to A 2A R-D 2 R heterodimer antagonism.

Fatigue is a non-motor symptom of Parkinson's disease (PD). Adenosine 2A receptor (A 2A R) and compromised dopamine neurotransmission are linked to fatigue. Studies demonstrate that A 2A R antagonism potentiates dopamine transmission via dopamine receptor D 2 (D 2 R). However, the heterodimer form of A 2A R-D 2 R in the striatum prompted questions about the therapeutic targets for PD patients. This study investigates the effects of caffeine (A 2A R non-selective antagonist) plus haloperidol (D 2 R selective antagonist) treatment in the fatigue induced by the reserpine model of PD. Reserpinized mice showed impaired motor control in the open field test (p < 0.05) and fatigue in the grip strength meter test (p < 0.05). L-DOPA and caffeine plus haloperidol similarly increased motor control (p < 0.05) and mitigated fatigue (p < 0.05). Our results support the A 2A R-D 2 R heterodimer participation in the central fatigue of PD, and highlight the potential of A 2A R-D 2 R antagonism in the management of PD.