Summary
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 μmol/l. Higher concentrations caused an increase in basal efflux of tritium. 8-OH-DPAT (1 μmol/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-HT1A binding site may not correspond to the 5-HT autoreceptor.
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Middlemiss, D.N. 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. Naunyn-Schmiedeberg's Arch. Pharmacol. 327, 18–22 (1984). https://doi.org/10.1007/BF00504986
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DOI: https://doi.org/10.1007/BF00504986