In mice pretreated intracerebroventricularly (i.c.v.) with
6-hydroxydopamine (6OHDA) (50 micrograms per mouse), as soon as the
hypothermia elicited by the
neurotoxin had vanished (3 hr), the hypothermic effect induced by the direct D2
dopamine receptor agonist RU 24926 (1 mg/kg, s.c.), was almost completely suppressed. This reduction in hypothermic effect was observed more than 1 month after the 6OHDA injection. On the 3rd day after 6OHDA injection, this reduction was observed for all tested doses of
RU 24926 (0.25-2 mg/kg). It was prevented when an i.p. administration of the
norepinephrine uptake inhibitor
desipramine (20 mg/kg) was performed 30 min before the 6OHDA i.c.v. injection. It was not modified when an i.p. administration of the
dopamine uptake inhibitor
GBR 12783 (20 mg/kg) was performed 30 min before the 6OHDA i.c.v. injection. The 6OHDA i.c.v. injection modified significantly neither the
dopamine nor the
serotonin hypothalamic contents. On the contrary it resulted in a marked decrease (-73%) of the
norepinephrine hypothalamic content, which was unchanged by the administration of
GBR 12783 (20 mg/kg, i.
p.) 30 min before 6OHDA, but completely prevented by
desipramine (20 mg/kg, i.
p.) 30 min before 6OHDA i.c.v. injection. It is concluded that the hypothermic effect resulting from the stimulation of D2
dopamine receptors involves a central
norepinephrine transmission, which is very rapidly altered after 6OHDA administration.