Using a batch method for incubation of hippocampal slices, we have examined the effects of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU24969) and (m-trifluoromethylphenyl)piperazine (TFMPP) on release of endogenous 5-hydroxytryotamine (5-HT). Release of 5-HT from slices was enhanced by RU24969 and TFMPP at concentrations from 1 to 10 mumols. The 5-HT uptake inhibitors imipramine and fluoxetine, but not the autoreceptor antagonist methiothepin, blocked the enhancement in 5-HT. These results suggest that RU24969 and TFMPP, previously identified as potent agonists at the nerve terminal autoreceptor, also interact at higher concentrations with the reuptake carrier to enhance extracellular levels of 5-HT.
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