In naive mice, the selective D1 agonist,
SK&F 38393 (7.5-30 mg/kg s.c.), induced a significant rise of body temperature (0.5-1 degree C) which was antagonized by
SCH 23390 (100 micrograms/kg s.c.) and by
flupenthixol (0.4 mg/kg i.p.). In mice treated with
reserpine (5 mg/kg s.c.) 18 h before testing, which on its own caused intense
hypothermia (10-12 degrees C),
SK&F 38393 (1.87-30 mg/kg s.c.) induced a dose-dependent and more marked rise of body temperature (5-7 degrees C). Similarly,
SK&F 38393 (30 mg/kg s.c.) partially prevented
reserpine-
induced hypothermia. The central origin of the
SK&F 38393 effects in
reserpine-treated mice is indicated by the rise of body temperature induced by the i.c.v. administration of the
drug (12.5-50 micrograms per mice). The SK&F 38393-induced rise of body temperature in acutely reserpinized mice was antagonized by
SCH 23390 (50-200 micrograms/kg s.c.),
clozapine (1.87-30 mg/kg i.p.) or
chlorpromazine (2-32 mg/kg i.p.) but not by
metoclopramide (25 or 100 mg/kg i.p.) or
amisulpride (12.5 or 50 mg/kg). In naive mice,
apomorphine (1 mg/kg s.c.) or
LY 171555 (0.4 mg/kg s.c.)
induced hypothermia which was antagonized by
amisulpride (12.5 mg/kg i.p.); a transiently increased body temperature was even measured 30 min after
apomorphine injection in
amisulpride-treated mice.
Apomorphine (1 mg/kg s.c.) induced a rise of body temperature in acutely reserpinized mice which was significantly reduced by
SCH 23390 (50 and 200 micrograms/kg s.c.) and significantly increased by
amisulpride (12.5 and 50 mg/kg i.p.). These data suggest that pharmacologically different
dopamine receptor subtypes mediate different effects on body temperature in mice: D1
dopamine receptors mediate a rise of body temperature which is increased in hypothermic reserpinized animals and
dopamine receptors of the D4 subtype mediate the decrease of body temperature in naive mice.