Effects of 21 days treatment with fluoxetine on stimulated endogenous 5-hydroxytryptamine overflow in the rat dorsal raphe and suprachiasmatic nucleus studied using fast cyclic voltammetry in vitro.
Changes in the extracellular concentration of 5-HT evoked by electrical stimulation of brain slices containing either dorsal raphe nucleus (DRN) or suprachiasmatic nucleus (SCN) from rats treated for 21 days with fluoxetine (5 mg/kg; i.p.) or water were monitored using fast cyclic voltammetry (FCV). Stimulated 5-HT overflow was enhanced significantly in both brain regions after 21 days treatment with fluoxetine but there was no change in the half time for re-uptake (t1/2). Concentration response curves for inhibition of electrically stimulated 5-HT overflow by 8-OH-DPAT (5-HT1a receptor agonist) or RU24969 (5-HT1b receptor agonist) in the DRN or SCN respectively were obtained in slices prepared from both groups of animals. There was a significant shift to the right in the dose-response curve for RU24969 in the SCN in fluoxetine treated animals but a shift to the left for the dose-response curve for 8-OH-DPAT in the DRN. These data suggest that down regulation of the 5-HT1b autoreceptors occurs in an axon terminal region (SCN) but that there is a sensitisation of 5-HT1a autoreceptor mechanisms controlling 5-HT overflow in the DRN.
O'Connor
J J
JJ
Department of Pharmacology, Queen Mary and Westfield College, London, UK.
Kruk
Z L
ZL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004558:Electric Stimulation; D004594:Electrophysiology; D005473:Fluoxetine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism*
D007211:Indoles; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D008719:Methiothepin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin