Identification of 5-hydroxytryptamine7 receptor binding sites in rat hypothalamus: sensitivity to chronic antidepressant treatment.
Due to the high level of expression of mRNA for the 5-hydroxytrytamine (5-ht7) 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-ht7 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-ht7 receptors but prevents the binding of [3H]5-HT to 5-HT1A and 5-HT1B 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-ht7 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-ht7 receptor binding sites. These data suggest that the 5-ht7 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.
Sleight
A J
AJ
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Carolo
C
C
Petit
N
N
Zwingelstein
C
C
Bourson
A
A
D000818:Animals; D001665:Binding Sites; D015536:Down-Regulation / Q000187:drug effects; D005473:Fluoxetine / Q000378:metabolism / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism / Q000648:ultrastructure*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D010869:Pindolol / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000378:metabolism; D014316:Tritium
D011985:Receptors, Serotonin; D005473:Fluoxetine; D014316:Tritium; D012701:Serotonin; D010869:Pindolol