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A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters.

Abstract：

BACKGROUND:Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT. Serotonergic effects occur with lower doses, whereas both serotonergic and noradrenergic effects occur with higher doses of venlafaxine. Chronic treatment of rats with selective serotonin reuptake inhibitors decreases SERT binding sites, whereas similar treatment with selective norepinephrine reuptake inhibitors decreases NET binding sites. We hypothesized that venlafaxine would affect monoamine transporters dose-dependently, with low doses causing selective reduction of SERT binding sites and higher doses reducing both SERT and NET binding sites. METHODS:Rats were treated for 21 days with a low (15 mg/kg/day) or high (70 mg/kg/day) dose of venlafaxine, vehicle, or other antidepressants. The SERT and NET density was determined by quantitative autoradiography. RESULTS:Neither dose of venlafaxine nor amitriptyline reduced binding to either the SERT or NET. In rats with noradrenergic terminals destroyed by 6-hydroxydopamine, venlafaxine still failed to reduce SERT binding. Also, rats treated simultaneously with sertraline plus desipramine exhibited reductions in both SERT and NET binding. CONCLUSIONS:Chronic venlafaxine treatment affected SERT and NET binding differently from paroxetine or desipramine. The inability of venlafaxine to reduce SERT or NET binding sites is not due to its dual uptake inhibiting properties.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Gould GG,Altamirano AV,Javors MA,Frazer A

doi

10.1016/j.biopsych.2005.07.011

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

408-14

issue

5

eissn

0006-3223

issn

1873-2402

pii

S0006-3223(05)00864-4

journal_volume

59

pub_type

杂志文章

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