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.