Akathisia is a subset of the larger
antipsychotic side effect profile known as extrapyramidal syndrome (EPS). It is associated with
antipsychotic treatment and is characterized as a feeling of inner
restlessness that results in a compulsion to move. There are currently no primate models available to assess
drug-induced akathisia; the present research was designed to address this shortcoming. We developed a novel rating scale based on both the Barnes
Akathisia Rating Scale (BARS) and the Hillside
Akathisia Scale (HAS) to measure the objective, observable incidence of
antipsychotic-induced
akathisia-like behavior in Cebus apella non-human primates (NHPs). To induce
akathisia, we administered the atypical
antipsychotic aripiprazole (1 mg/kg) or the selective
phosphodiesterase 10A (PDE10A) inhibitor MP-10 (1-3 mg/kg). Treatment with both compounds produced significantly greater
akathisia scores on the rating scale than vehicle treatment. Characteristic behaviors observed included vocalizations, stereotypies, teeth grinding, restless limb movements, and hyperlocomotion.
Adenosine A2A receptor antagonists have previously been shown to be effective in blocking
antipsychotic-induced EPS in primates. The selective A2A receptor antagonist,
SCH 412348 (10-30 mg/kg), effectively reduced or reversed
akathisia-like behavior induced by both
aripiprazole and MP-10. This work represents the first NHP measurement scale of
akathisia and demonstrates that NHPs are responsive to
akathisia-inducing agents. As such, it provides a useful tool for the preclinical assessment of putative
antipsychotics. In addition, these results provide further evidence of the utility of A2A receptor antagonists for the treatment of
antipsychotic-induced
movement disorders.