Rapid desensitization of 5-HT₁ receptors by incubation of rat hippocampal slices with agonist in vitro

The effect of incubation with agonist on the 5-HT (5-hydroxytryptamine, serotonin) receptors of rat hippocampus was investigated by use of hippocampal slices in vitro followed by measurement of ligand-binding properties using ³H-labelled 5-HT. Slices were incubated for 90 minutes in physiological medium containing 'cold' 5-HT at a concentration of 0.1 mM and then thoroughly rinsed. A crude tissue extract was made and binding of ³H-5-HT determined using 'cold' agonist at 0.01 mM to discriminate specific binding to receptors of the 5-HT₁ subtype. Slices which had been pre-incubated with agonist showed a significant reduction (circa 25% of controls) in maximum density of binding sites. There was no effect of pre-incubation with agonist on the affinity of these receptors or on the non-specific binding of the radio-ligand.