Aj. Sleight et al., IDENTIFICATION OF 5-HYDROXYTRYPTAMINE(7) RECEPTOR-BINDING SITES IN RAT HYPOTHALAMUS - SENSITIVITY TO CHRONIC ANTIDEPRESSANT TREATMENT, Molecular pharmacology, 47(1), 1995, pp. 99-103
Due to the high level of expression of mRNA for the 5-hydroxy-tryptami
ne (5-ht(7)) receptor in the hypothalamus and the high affinity of 5-H
T for this receptor, [H-3]5-HT binding was performed in rat hypothalam
us 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 b
inding 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 hypoth
alamic binding site to correlate well with the published pharmacology
of the 5-ht(7) receptor (r = 0.921). The treatment of rats with fluoxe
tine (5 mg/kg/day, orally) for 21 days caused a significant reduction
in the number of hypothalamic 5-ht(7) receptor binding sites. These da
ta suggest that the 5-ht(7) receptor binding site is expressed in rat
hypothalamus and that this receptor binding site is down-regulated aft
er a chronic increase in the synaptic level of 5-HT.