Animal models of acute drug-induced akathisia - a review

Akathisia is a complex neurobehavioural side effect of neuroleptics and som e other drugs which is characterised by subjective report and objective man ifestations of restlessness. Its pathophysiology is poorly understood and t here are many limitations to its investigation in humans. This paper review s the various attempts that have been made in modelling acute akathisia in animals. Homologous as well as isomorphic models have been attempted, but m ost models are partial as they reproduce either the subjective or the objec tive features of the syndrome. None of the available models has bren fully validated. Neuroleptic-induced defecation in the rat, even though constrain ed by a lack of symptom similarity and thereby face validity, has been most studied as a model of subjective akathisia. Rat models of restlessness, in particular those involving the use of serotonergic drugs or lesions of the veneral tegmentum or medial prefrontal cortex, are interesting partial mod els that should be further investigated. Neuroleptic-induced akathisia is o bserved in primates and has been modelled in dogs, and these should be stud ied further for their validation. It is also necessary to consider the subt ypes of akathisia in the attempts to develop these models. (C) 2000 Elsevie r Science Ltd. All rights reserved.