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

被引:43
作者
Gould, GG
Altamirano, AV
Javors, MA
Frazer, A
机构
[1] Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA
[2] Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA
[3] S Texas Vet Hlth Care Syst, San Antonio, TX USA
关键词
serotonin transporter; norepinephrine transporter; dual uptake inhibitor; venlafaxine; amitriptyline; quantitative autoradiography;
D O I
10.1016/j.biopsych.2005.07.011
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 NET binding sites. We hypothesized 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. 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. 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. Alsom rats treated simultaneously with sertraline plus desipramine exhibited reductions in both SERT and NET binding. 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.
引用
收藏
页码:408 / 414
页数:7
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