Intermittent treatment with droperidol, a short-acting neuroleptic, increases behavioral dopamine receptor sensitivity.

Drug holidays have been proposed as a preventive strategy against the development of tardive dyskinesia. Three animal studies in which dopamine receptor hypersensitivity after chronic neuroleptic treatment was used as a model for tardive dyskinesia failed to find any reduction in dopamine receptor hypersensitivity with intermittent, as opposed to continuous, treatment. Since most neuroleptics have a long half-life in vivo, we hypothesized that truly drug-free periods may not have been achieved in previous studies. Droperidol, an ultrashort-acting butyrophenone neuroleptic, was administered to rats for 22 days in twice-daily injections or one injection every 48 hours. At 60 hours after the last dose there was no difference in apomorphine-induced stereotypy between continuously treated and intermittently treated animals. Thus, even totally drug-free periods do not reduce the development of dopamine receptor hypersensitivity.