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Neuropharmacology. 1982 Jul;21(7):663-9.

Circadian changes in the destruction and effects of haloperidol in the rat.


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.

[PubMed - indexed for MEDLINE]
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