A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters.
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.
Gould
Georgianna G
GG
Department of Pharmacology, University of Texas Health Science Center at San Antonio, Texas 78229-3900, USA. gouldg@uthscsa.edu
Altamirano
Alfonso V
AV
Javors
Martin A
MA
Frazer
Alan
A
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D003511:Cyclohexanols / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000187:drug effects*; D017374:Paroxetine / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects*; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D000639:Amitriptyline; D017374:Paroxetine; D000069470:Venlafaxine Hydrochloride; D003891:Desipramine