J. Viyoch et al., Dosing time-dependent tolerance of catalepsy by repetitive administration of haloperidol in mice, J PHARM EXP, 298(3), 2001, pp. 964-969
Citations number
32
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
To investigate the effect of repeated administration time on the developmen
t of tolerance, male ICR mice, housed under 12: 12-h light/dark cycle (7:00
AM, lights on), were treated with haloperidol 4 mg/kg/day i.p. at 9:00 AM
or 9:00 PM, the time nearly corresponding to the maximal or minimal catalep
sy responses to a single dose, respectively, for 14 days and catalepsy resp
onses were monitored at 1 h after administration each day. The findings ind
icated that, on day 1 to day 6, a greater development of tolerance was seen
in the group of mice treated at 9:00 AM, and catalepsy behavior exhibited
a significant difference between the two dosing times (P < 0.01). The study
of D-2 receptor mRNA expression in mouse striatum revealed that the phase
of D-2 receptor mRNA rhythm was similar to that of catalepsy response, with
the maximum around mid-light and the minimum around mid-dark. After repeat
ed administration, the increase in D-2 receptor mRNA levels in mice treated
with haloperidol at 9:00 AM was higher than that of mice treated with halo
peridol at 9:00 PM. In addition, from a [H-3]spiperone binding study, the a
mount of binding site [H-3]spiperone after repeated injection of haloperido
l at 9:00 AM was greater than that after repeated injection at 9:00 PM. The
se findings demonstrate the importance of dosing time on the susceptibility
to extrapyramidal effects and the relation of administration time to D-2 r
eceptor change and tolerance.