Involvement of norepinephrine neurons in the hypothermia induced by intracerebroventricular administration of 6-hydroxydopamine in mice, evidenced by antidepressants

Summary

The intracerebroventricular (i.c.v.) administration of increasing doses of 6-hydroxydopamine (6OHDA) (12.5–50 μg) induces in mice a dose-dependent hypothermic effect. This hypothermic effect is not affected either by serotonin uptake inhibitors (indalpine, clomipramine, trazodone, fluoxetine) or by dopamine uptake inhibitors (GBR 12783, amineptine). On the contrary, the hypothermia is partly antagonized by norepinephrine uptake inhibitors (desipramine, nomifensine, viloxazine, maprotiline, protryptiline), as well as amfonelic acid. The antagonism elicited by desipramine is observed when the drug is administered intraperitoneally (from 5 mg/kg) or intracerebroventricularly (from 5 μg per mouse). 6-hydroxydopamine-induced hypothermia is antagonized by imipramine after a time lag of 1 hour; this antagonism lasts 6–11 hours after intraperitoneal administration of the drug (20 mg/kg). The hypothermic effect of 6-hydroxydopamine is diminished by a previous 6-hydroxydopamine i.c.v. administration (50 μg, 7 days before), except in mice pretreated with desipramine at the time of the first 6-hydroxydopamine injection. The hypothermic effect is completely abolished by two previous 6-hydroxydopamine i.c.v. administrations (50 μg, 7 days interval). It is also decreased in mice receiving DSP4 15 days before testing (50 mg/kg, i.p.). Finally, neither haloperidol (0.5 mg/kg i.p.) nor SCH 23390 (100 μg/kg s.c.) antagonize 6-hydroxydopamine-induced hypothermia. It is concluded that this effect is largely depending on central norepinephrine neurons.