Effect of daily dose of chronic haloperidol and chronic apomorphine on behavioral hypersensitivity in the rat.

Behavioral hypersensitivity in the rat consisting of increased dopamine-mediated stereotypic behaviors has been found to follow a 10-day course of treatment with the neuroleptic haloperidol as well as with the direct dopamine agonist apomorphine. The daily dose versus response relationship for chronic haloperidol indicates that a threshold daily dose exists and that behaviors increase with increasing daily dose. On the other hand, low rather than high daily doses of chronic apomorphine induce behavioral hypersensitivity and the response decreases with increasing daily dose. Prolonged functional denervation of striatal postsynaptic dopamine receptors by either neuroleptic blockade or autoreceptor stimulation may explain these findings. The results may help elucidate the relative risk of daily neuroleptic dose on tardive dyskinesia development and indicate a possible mechanism for chronic agonist-associated side effects like L-Dopa dyskinesias.