8-Hydroxy-2-(di-n-propylamino) tetralin is devoid of activity at the 5-hydroxytryptamine autoreceptor in rat brain. Implications for the proposed link between the autoreceptor and the [3H] 5-HT recognition site.
Experiments have been carried out to provide direct evidence for the proposed presynaptic 5-HT autoreceptor agonist activity of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) a compound with selectivity for the 5-HT1A subtype of the 5-HT1 binding site. Rat brain frontal cortex slices were preincubated with [3H] 5-hydroxytryptamine and continuously stimulated with Krebs solution containing paroxetine and elevated K+ ions (25 mmol/l). The elevated efflux of tritium caused by exposure to K+ Krebs was inhibited in a dose related manner by 5-hydroxytryptamine and this inhibition was attenuated in the presence of quipazine and methiothepin. In slices of the rat frontal cortex, 8-OH-DPAT was without agonist or antagonist activity at the 5-HT autoreceptor at concentrations up to 1 mmol/l. Higher concentrations caused an increase in basal efflux of tritium. 8-OH-DPAT (1 mumol/l) was also without inhibitory activity in the piriform cortex, striatum and the hippocampus. These experiments have therefore failed to provide direct evidence for agonist activity of 8-OH-DPAT at the 5-HT autoreceptor and alternative explanations must be sought for its biochemical and behavioural effects in vivo. Moreover, the fact that 8-OH-DPAT is inactive at the autoreceptor at concentrations selective for the 5-HT1A recognition site suggests that this subtype of the 5-HT1 binding site may not correspond to the 5-HT autoreceptor.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014316:Tritium
D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D014316:Tritium; D012701:Serotonin; D011814:Quipazine; D008719:Methiothepin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011188:Potassium