Abstract |
The intracerebroventricular (i.c.v.) administration of increasing doses of 6-hydroxydopamine (6OHDA) (12.5-50 micrograms) 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 microgram 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 micrograms, 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 micrograms, 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 SCH23390 (100 micrograms/kg s.c.) antagonize 6-hydroxydopamine-induced hypothermia. It is concluded that this effect is largely depending on central norepinephrine neurons.
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Authors | I Leroux-Nicollet, C Panissaud, J Costentin |
Journal | Journal of neural transmission
(J Neural Transm)
Vol. 74
Issue 1
Pg. 17-27
( 1988)
Austria |
PMID | 2971783
(Publication Type: Journal Article)
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Chemical References |
- Antidepressive Agents
- Hydroxydopamines
- Neurotransmitter Uptake Inhibitors
- Oxidopamine
- Desipramine
- Norepinephrine
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Topics |
- Animals
- Antidepressive Agents
(pharmacology)
- Brain
(drug effects, metabolism, physiopathology)
- Desipramine
(pharmacology)
- Dose-Response Relationship, Drug
- Hydroxydopamines
- Hypothermia
(chemically induced, metabolism)
- Injections, Intraventricular
- Male
- Mice
- Neurotransmitter Uptake Inhibitors
(pharmacology)
- Norepinephrine
(metabolism, physiology)
- Oxidopamine
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