Abstract

Striking circadian changes in behavioral sensitivity to haloperidol were found by measurements of cataleptic responses in rats trained in a controlled lighting cycle (lights on, 7:00 a.m.--7:00 p.m.). Thus, catalepsy was maximal at about 4:00 p.m. and minimal at about 4:00 a.m., virtually the opposite of the circadian rhythm of spontaneous behavioral activity in drug-free rats. At a given dose of haloperidol, catalepsy scores differed 2- to 3-fold, and the ED50 shifted left nearly 10-fold from a.m. to p.m. After fixed doses of haloperidol, tissue levels of the drug, as determined by a sensitive and selective radioreceptor assay, differed by 2- to 6-fold through the 24 hr cycle and brain levels closely followed the circadian changes in behavior. These results suggest a pharmacokinetic contribution to the circadian changes in behavioral response, although additional pharmacodynamic factors are also considered.

View details for Web of Science ID A1982PB21200009

View details for PubMedID 6889690