Effects of protriptyline on the depletion of catecholamines induced by 6-hydroxydopamine in the brain of the rat

Evetts, K. D.; Iversen, Leslie L.

doi:10.1111/j.2042-7158.1970.tb10564.x

Cited by 66 publications

(9 citation statements)

References 13 publications

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“…p-Chloroamphetarnine and 6-0HDA appear to use the uptake carriers of 5-HT and NE, respectively, to en ter the corresponding nerve terminals before initiation of depletion of the monoamines and decreases of up take activities due to neurotoxicity (Evetts and Iversen 1970;Meek et al 1971;. Fluoxe tine, a selective inhibitor of 5-HT uptake, blocks only the p-CA-induced depletion of 5-HT, with an E050 of 1.21lmollkg IP , while tomoxe tine, a selective inhibitor of NE uptake, blocks only the 6-0HOA-induced depletion of NE in heart with an E050 of 5.8llmollkg IP .…”

Section: Food Intake Studiesmentioning

confidence: 99%

LY248686, A New Inhibitor of Serotonin and Norepinephrine Uptake

Wong

Bymaster

Mayle

et al. 1993

Neuropsychopharmacol

209

136

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LY248686 is an inhibitor of serotonin (S-hydroxytryptamine; 5-HT) and norepinephrine (NE) uptake in synaptosomal preparations of hypothalamus and cerebral cortex, and 5-HT uptake in human blood platelets, with inhibitor constants near nanomolar concentrations. Upon administration to rats 1 hour before sacrifi ce, LY248686 caused dose-dependent and parallel decreases of 5-HT and NE uptake in hypothalamus homogenates ex vivo. LY248686 is a positive enantiomer and was slightly more potent than its negative isomer, LY248685, as an inhibitor of 5-HT uptake. Both isomers were only weak inhibitors of dopamine (DA) uptake in striatal synaptosomes. The inhibitory effects on 5-HT and NE uptake after a single administration of LY248686 KEY WORDS: Uptake; Inhibitor; Serotonin; Norepineph rineThe extent of inhibition of serotonin (5-hydroxytrypta mine; 5-HT) and norepinephrine (NE) uptake by the tricyclic tertiary amine-containing antidepressant drugs depends on their relative degrees of metabolic N-demethylation. Amitriptyline, an inhibitor of 5-HT and NE uptake in nerve-ending preparations (synap tosomes), is converted in vivo to nortriptyline, a po tent and selective inhibitor of NE uptake, while imipra mine, a selective inhibitor of 5-HT uptake, is converted to desipramine, another potent and selective inhibitor

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Section: Food Intake Studiesmentioning

confidence: 99%

LY248686, A New Inhibitor of Serotonin and Norepinephrine Uptake

Wong

Bymaster

Mayle

et al. 1993

Neuropsychopharmacol

209

136

View full text Add to dashboard Cite

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“…The above-mentioned data prove that the intraventricular route of 6-OHDA administration is adequate to study the catecholaminergic effect on pituitary secretion and proliferation. The pretreatment of animals with DMIa blocker of NE uptakeretards the destruction of noradrenergic fibers without altering the ability of 6-OHDA to destroy dopaminergic neurons (Breese, 1975;Breese and Cooper, 1977;Breese and Traylor, 1971;Evetts and Iversen, 1970).…”

Section: Discussionmentioning

confidence: 99%

Effects of intraventricular injections of 6‐hydroxydopamine on anterior pituitary cell proliferation

Lewiński¹,

Konopacki

Pawlikowski³

et al. 1984

Anat. Rec.

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Effects of intraventricular injections of 6-hydroxydopamine (6-OHDA; 200 micrograms/20 microliter vehicle) on anterior pituitary cell proliferation in rats have been investigated by means of the colchicine metaphase-arrest technique. In those groups of animals receiving 6-OHDA alone or 6-OHDA plus desmethylimipramine (DMI, 25 mg/kg body weight i.p.), where the mean mitotic activity rates (MMARs) were initially low at 48 hours, an increase of MMARs was observed at 96 and 144 hours after the drug injections. At 144 hours after drug administration, the MMARs values in the 6-OHDA-injected group and in the 6-OHDA + DMI-treated group were significantly higher than those in the control groups. This increase of MMARs resulted from the enhancement of acidophilic and chromophobe cell proliferation. The low MMARs at 48 hours after 6-OHDA injection are probably a result of dopamine release from damaged nerve endings; the enhancement of MMARs (particularly evident in the 6-OHDA + DMI-treated group) at 96 and 144 hours after drug administration is presumably related to a deficiency of dopaminergic control of anterior pituitary cell proliferation.

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“…The introduction of the chemotoxic substances, 6-hydroxydopamine (6-OHDA) and the dihydroxytryptamines, which permit the selective destruction of catecholaminergic and serotonergic neurons respectively, as well as elaboration of procedures for relatively selective destruction of dopaminergic or noradrenergic neurons (Evetts and Iversen, 1970;Breese and Taylor, 1971) have provided new approaches to this problem. It has been established that intracerebroventricularly (i.c.v.)…”

Section: Introductionmentioning

confidence: 99%

The functional role of the noradrenergic neurons in the thermoregulatory circuits in mice

Schelkunov

Andreeva

Korovin

et al. 1981

J. Neural Transmission

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Intracerebroventricular (i.c.v.) treatment of mice with 6-hydroxydopamine (6-OHDA; 20--50 micrograms per mouse), which depletes brain noradrenaline (NA) and DA, completely prevents or significantly diminishes the hypothermic effect of various classes of drugs: dopaminomimetics--apomorphine (0.5--10 mg/kg), piribedil (40--100 mg/kg), bromocriptine (3 to 10 mg/kg), CM 29-712 (2--10 mg/kg), d, l-amphetamine (1--2 mg/kg), and L-DOPA (10--100 mg/kg) in combination with Ro 4-4602 (5--40 mg/kg); cholinomimetics--oxotremorine (0.04--0.05 mg/kg), arecoline (5--10 mg/kg) and pilocarpine (2--3 mg/kg); neuroleptics--chlorpromazine, promazine, perphenazine, chlorprothixene, haloperidol, fluanisone (5--10 mg/kg); central alpha-adrenoblocker aceperone (20--40 mg/kg); inhibitor of tyrosine-hydroxylase alpha-methyltyrosine (200--300 mg/kg); inhibitor of dopamine-beta-hydroxylase--disulfiram (150--250 mg/kg) and FLA-63 (15--25 mg/kg). This antihypothermic effect was demonstrated up to 3 months after administration of 6-OHDA for DA-mimetics and neuroleptics and up to 3 weeks for cholinomimetics. The hypothermic effect of presumable GABA-mimetics Phenybut (100--150 mg/kg) and Lioresal (10--25 mg/kg) was enhanced by a prior 6-OHDA treatment. Pretreatment of mice with desipramine (25 to 30 mg/kg i.p.), protriptyline (20 mg/kg) or AW 15(1)1129 (15--20 mg/kg) 20--45 min before 6-OHDA administration protects the central NA-ergic neurons from a destructive effect of 6-OHDA and partially or completely counteracts the antihypothermic as well as prohypothermic (in the case of GABA-mimetics) effect of 6-OHDA. In rats desipramine counteracted antihypothermic effect of 6-OHDA in the case of piribedil, but not of apomorphine. Intracerebroventricular treatment of mice with a low (15 microgram) dose of 5, 6-dihydroxytryptamine (5, 6-DHT) enhanced the hypothermic effects of DA-mimetics; higher doses of 5, 6-DHT (26 and 30 micrograms) and 5, 7-DHT (40 and 46 micrograms) diminished the hypothermic effects; the antihypothermic effect of 6-OHDA was stronger than that of equimolar doses of 5, 6- or 5,7-DHT; desipramine pretreatment counteracted antihypothermic effects of 5, 6-DHT and 5, 7-DHT as well as depletion of brain NA they produce. The data presented reveal the key position for NA-ergic neurons in a temperature regulation and, particularly, in effects of various drugs on body temperature in mice. The tentative fragment of the neuronal thermoregulatory circuit is proposed in attempt to account for the presented an other known data concerning drug action (and interactions) on core temperature in mice.

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Effects of protriptyline on the depletion of catecholamines induced by 6-hydroxydopamine in the brain of the rat

Cited by 66 publications

References 13 publications

LY248686, A New Inhibitor of Serotonin and Norepinephrine Uptake

LY248686, A New Inhibitor of Serotonin and Norepinephrine Uptake

Effects of intraventricular injections of 6‐hydroxydopamine on anterior pituitary cell proliferation

The functional role of the noradrenergic neurons in the thermoregulatory circuits in mice

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