Venlafaxine: acute and chronic effects on 5-hydroxytryptamine levels in rat brain in vivo.
Venlafaxine is a dual serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline uptake inhibitor which has been claimed to have an onset of antidepressant action which is faster than for other comparable drugs. The effects of venlafaxine on brain 5-HT levels in vivo have not yet been examined. Acute administration of venlafaxine to rats by i.p. injection resulted in dose-dependent increases in cortical and hippocampal 5-HT levels, as measured by in vivo microdialysis, over the range 5-20 mg/kg. The effect of venlafaxine (10 mg/kg i.p.) was potentiated by prior administration of pindolol (10 mg/kg s.c.) in hippocampus but not in frontal cortex. Daily administration of venlafaxine (5 mg/kg i.p.) for 4 weeks did not change basal 5-HT levels in either brain area. The effect of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.2 mg/kg s.c.) to reduce 5-HT levels was unaffected by chronic venlafaxine at this dose, indicating that there was no change in sensitivity of presynaptic 5-HT1A autoreceptors.
Gur
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E
Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Dremencov
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E
Lerer
B
B
Newman
M E
ME
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003511:Cyclohexanols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D000069470:Venlafaxine Hydrochloride
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003511:Cyclohexanols; D010869:Pindolol; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride