Sibutramine induces potential-dependent exocytotic release but not carrier-mediated release of dopamine and 5-hydroxytryptamine

Kiyoharu Ukai, Terutake Nakagawa, Tadashi Ohyama, Hiroshi Nakanishi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In order to clarify the mechanism underlying the anti-obesity effects of sibutramine, we examined the effects of sibutramine on extracellular levels of dopamine and 5-hydroxytryptamine (5-HT) through microdialysis in the striatum in unanesthetized and freely moving rats. Sibutramine (5 mg/kg, oral administration (p.o.)) increased extracellular dopamine and 5-HT levels in rat striatum. The tricyclic antidepressant dosulepin (80 mg/kg, p.o. or 1 μM perfusion through the striatal probe) increased 5-HT levels only. Sibutramine-induced dopamine release was antagonized by perfusion of tetrodotoxin (1 μM) through the microdialysis probe in the striatum. However, sibutramine-induced dopamine release was not inhibited by prazosin (1 mg/kg, intraperitoneal injection (i.p.)), a suppressor of serotonergic activity in the striatum via blockade of α1-adrenoceptors, or perfusion with nomifensine (1 μM), an inhibitor of dopamine re-uptake. These results suggest that sibutramine increases dopamine levels in the striatum by exocytotic release and not by a carrier-mediated mechanism.

Original languageEnglish
Pages (from-to)209-215
Number of pages7
JournalEuropean Journal of Pharmacology
Volume484
Issue number2-3
DOIs
Publication statusPublished - Jan 26 2004

Fingerprint

sibutramine
Dopamine
Serotonin
Perfusion
Microdialysis
Dothiepin
Dopamine Uptake Inhibitors
Nomifensine
Corpus Striatum
Tricyclic Antidepressive Agents
Prazosin
Tetrodotoxin
Intraperitoneal Injections
Adrenergic Receptors
Oral Administration
Obesity

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Sibutramine induces potential-dependent exocytotic release but not carrier-mediated release of dopamine and 5-hydroxytryptamine. / Ukai, Kiyoharu; Nakagawa, Terutake; Ohyama, Tadashi; Nakanishi, Hiroshi.

In: European Journal of Pharmacology, Vol. 484, No. 2-3, 26.01.2004, p. 209-215.

Research output: Contribution to journalArticle

Ukai, Kiyoharu ; Nakagawa, Terutake ; Ohyama, Tadashi ; Nakanishi, Hiroshi. / Sibutramine induces potential-dependent exocytotic release but not carrier-mediated release of dopamine and 5-hydroxytryptamine. In: European Journal of Pharmacology. 2004 ; Vol. 484, No. 2-3. pp. 209-215.
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