IDENTIFICATION OF 5-HYDROXYTRYPTAMINE(7) RECEPTOR-BINDING SITES IN RAT HYPOTHALAMUS - SENSITIVITY TO CHRONIC ANTIDEPRESSANT TREATMENT

Due to the high level of expression of mRNA for the 5-hydroxy-tryptamine (5-ht(7)) receptor in the hypothalamus and the high affinity of 5-HT for this receptor, [H-3]5-HT binding was performed in rat hypothalamus to determine whether 5-ht(7) receptor binding sites are present in animal tissue. [H-3]5-HT binding was performed in the presence of 100 nM pindolol, which is inactive at 5-ht(7) receptors but prevents the binding of [H-3]5-HT to 5-HT1A and 5-HT1B receptor binding sites. Under these conditions, [H-3]5-HT bound to a binding site with an affinity of 1.94 nM. Displacement studies showed the pharmacology of the hypothalamic binding site to correlate well with the published pharmacology of the 5-ht(7) receptor (r = 0.921). The treatment of rats with fluoxetine (5 mg/kg/day, orally) for 21 days caused a significant reduction in the number of hypothalamic 5-ht(7) receptor binding sites. These data suggest that the 5-ht(7) receptor binding site is expressed in rat hypothalamus and that this receptor binding site is down-regulated after a chronic increase in the synaptic level of 5-HT.