A Critical Evaluation of Behavioral Rodent Models of Motor Impairment Used for Screening of Antiparkinsonian Activity: The Case of Adenosine A2A Receptor Antagonists

Animal models of motor dysfunction constitute the basis for the screening of new drugs with potential efficacy in diseases characterized by motor impairment, such as Parkinson's Disease (PD). Taking adenosine A(2A) receptor antagonists as an example of a new class of drugs for PD, the review will examine the most utilized rodent models of motor impairment and the results reported in the literature with this class of drugs. The results obtained so far in rodent models of PD suggested that A(2A) receptor antagonists might have symptomatic therapeutic efficacy in PD. They may ameliorate initiation of movement, gait and muscle rigidity, sensorimotor integration deficits, and tremor. Moreover, A(2A) receptor antagonists when administered with a low sub-threshold dose of l-DOPA potentiated its efficacy. However, the clinical trials so far performed have evaluated their efficacy in the ON/OFF of PD patients with motor complications, showing a limited efficacy of this class of drug. Therefore, on one hand, animal models of PD might have a limited validity; on the other hand, clinical trials should explore the efficacy of A(2A) receptor antagonists on a broader range of parkinsonian conditions.