Perioral behaviors induced by cholinesterase inhibitors: a controversial animal model

Perioral behaviors induced by neuroleptic drugs have been interpreted as an animal model of tardive dyskinesia. However, these behaviors have also been induced or enhanced by physostigmine, a cholinesterase inhibitor. The latter result is contradictory to the clinical effect of physostigmine in human tardive dyskinesia. In view of this contradiction and other considerations, perioral behaviors have also been interpreted as a model of acute dystonia. The present experiments replicated an earlier failure to observe spontaneous perioral behaviors after long-term neuroleptic treatment in rats as well as the paradoxical effect of physostigmine. The effect of physostigmine was also compared to phenylmethanesulfonyl fluoride and methanesulfonyl fluoride, irreversible CNS active cholinesterase inhibitors. There were significant differences between the effects of the various cholinesterase inhibitors and their interactions with perioral behaviors and neuroleptic treatment. It is concluded that the effects of cholinesterase inhibitors on perioral behaviors in rodents may not be accounted for entirely by cholinesterase inhibition. Further experiments using additional agonists and antagonists will be required to clarify the behavioral effects of these cholinesterase inhibitors.