Trazodone increases extracellular serotonin levels in the frontal cortex of rats.

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Pazzagli M, Giovannini MG, Pepeu G

Trazodone increases extracellular serotonin levels in the frontal cortex of rats.

Eur J Pharmacol. 1999 Nov 3;383(3):249-57. doi: 10.1016/s0014-2999(99)00644-5.

PubMed ID

10594316 [ View in PubMed

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Abstract

The effects of the antidepressant drug, trazodone, on the extracellular 5-hydroxytryptamine (5-HT) levels in the frontal cortex of freely moving rats was investigated using microdialysis coupled to a high performance liquid chromatography (HPLC) detection method. Systemic administration of 1.25 and 2.5 mg/kg s.c. of trazodone was followed by a rise in the 5-HT level which reached a 5-fold peak over the basal level 5 h after injection, and a 3-fold peak after 1 h. Higher doses had no effect. The increase was prevented by pretreatment with fluoxetine (10 mg/kg s.c.), a 5-HT uptake inhibitor. Direct administration of trazodone (0.03, 0.1, 1, 2 microg/microl), by reverse dialysis into the frontal cortex, elicited a dose-dependent large increase in 5-HT levels. The increase was not prevented by systemic fluoxetine administration but was reduced by local perfusion of ketanserin (0.1 microg/microl) a 5-HT(2A/C) receptor antagonist. Trazodone s.c. administration for 7 days did not increase 5-HT basal levels but enhanced the effects of challenge doses of 2.5 and 5 mg/kg s.c. The present work demonstrated that trazodone increases the 5-HT extracellular level through a double mechanism which involves the 5-HT transporter and 5-HT(2A/C) receptors. This increase may trigger the chain of events which lead to the therapeutic effects, similar to the case of many other antidepressant drugs.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Trazodone	5-hydroxytryptamine receptor 2A	Protein	Humans	Yes	Antagonist	Details
Trazodone	5-hydroxytryptamine receptor 2C	Protein	Humans	Yes	Agonist	Details