RAPID AND LONG-LASTING REDUCTION OF THE HYPOTHERMIC EFFECT OF A D2 DOPAMINE AGONIST AFTER AN INTRACEREBROVENTRICULAR INJECTION OF 6-HYDROXYDOPAMINE

In mice pretreated intracerebroventricularly (i.c.v.) with 6-hydroxydo pamine (6OHDA) (50 mu g per mouse), as soon as the hypothermia elicite d by the neurotoxin had vanished (3 hr), the hypothermic effect induce d by the direct D2 dopamine receptor agonist RU 24926 (1 mg/kg, s.c.), was almost completely suppressed. This reduction in hypothermic effec t 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. admin istration of the norepinephrine uptake inhibitor desipramine (20 mg/kg ) was performed 30 min before the 6OHDA i.c.v. injection. It was not m odified when an i.p. administration of the dopamine uptake inhibitor G BR 12783 (20 mg/kg) was performed 30 min before the 6OHDA i.c.v. injec tion. The 6OHDA i.c.v. injection modified significantly neither the do pamine nor the serotonin hypothalamic contents. On the contrary it res ulted in a marked decrease (-73%) of the norepinephrine hypothalamic c ontent, 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 conclude d that the hypothermic effect resulting from the stimulation of D2 dop amine receptors involves a central norepinephrine transmission, which is very rapidly altered after 6OHDA administration.