Effects of chronically administered venlafaxine on 5-HT receptor activity in rat hippocampus and hypothalamus.
The effects of chronic administration of the mixed serotonin [5-hydroxytryptamine (5-HT)]/norepinephrine re-uptake inhibitor venlafaxine (5 mg/kg daily by osmotic minipump for 28 days) on the sensitivity of somatodendritic 5-HT(1A) autoreceptors on serotonergic neurons innervating the hypothalamus, and on 5-HT(1B) autoreceptors in both hypothalamus and hippocampus, were determined using in vivo microdialysis in freely moving rats. Venlafaxine induced a reduction in sensitivity of 5-HT(1B) autoreceptors in hypothalamus, but did not affect the sensitivity of 5-HT(1A) autoreceptors, or of 5-HT(1B) autoreceptors in hippocampus. The corticosterone and oxytocin responses to the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.05 or 0.2 mg/kg), a measure of postsynaptic 5-HT(1A) receptor activity in the hypothalamus, were reduced in animals administered 5 or 10 mg/kg venlafaxine daily by intraperitoneal injection for 21 days. This desensitization of post-synaptic 5- HT(1A) receptors in the hypothalamus may be a consequence of increased 5-HT levels induced by desensitization of the presynaptic 5-HT(1B) receptors. These results taken together with those of previous studies suggest that the hypothalamus might be an important site of drug action, and that venlafaxine has an overall mechanism similar to that of selective serotonin re-uptake inhibitors.
Gur
Eitan
E
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, PO Box 12000, 91120, Jerusalem, Israel.
Dremencov
Eliyahu
E
Van De Kar
Louis D
LD
Lerer
Bernard
B
Newman
Michael E
ME
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D003511:Cyclohexanols / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology; D010121:Oxytocin / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, 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; D003345:Corticosterone; D003511:Cyclohexanols; D010069:Oxadiazoles; D010121:Oxytocin; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; C090701:GR 127935