Diurnal variations of striatal D2 dopaminergic receptors and its relation with haloperidol-induced catalepsy

In spite of the clear evidences for the blockade of dopaminergic D2 recepto rs as the mechanism of action for haloperidol-induced catalepsy, the contri bution of pharmacokinetic and pharmacodynamic aspects on the diurnal modula tion of haloperidol-induced catalepsy is controversial. We studied the diur nal variations of striatal dopamine receptors and its relation with catalep sy diurnal variations. The [H-3]-spiperone binding to dopamine receptors ha d a clear rhythm with a peak at 00:00 to 03:00 h, and a trough at 12:00 to 18:00 h. Haloperidol-produced catalepsy measured with the four-cork test, a lso showed a clear rhythm, with a peak at 00:00 h and trough at 9:00 h. The dose-response curves at peak and trough of catalepsy had the same ED50 (0. 12 mg), with time-related changes in the maximal effect. Similar diurnal va riations between catalepsy and dopamine receptor binding, indicate a releva nt role of temporal pharmacodynamics of haloperidol on the modulation of it s behavioral effects.