Identification of 5-hydroxytryptamine7 receptor binding sites in rat hypothalamus: sensitivity to chronic antidepressant treatment
Sleight, A.J.; Carolo, C.; Petit, N.; Zwingelstein, C.; Bourson, A.
Molecular Pharmacology 47(1): 99-103
1995
ISSN/ISBN: 0026-895X PMID: 7838138 Document Number: 450718
Due to the high level of expression of mRNA for the 5-hydroxytryptamine (5-ht-7) receptor in the hypothalamus and the high affinity of 5-HT for this receptor, (3H)5-HT binding was performed in rat hypothalamus to determine whether 5-ht-7 receptor binding sites are present in animal tissue. (3H)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 (3H)5-HT to 5-HT-1A and 5-HT-1B receptor binding sites. Under these conditions, (3H)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.