Serotonin receptors in the brain of rats treated chronically with imipramine or RU24969: support for the 5-HT1B receptor being a 5-HT autoreceptor.
Rats were treated by intraperitoneal injection for four weeks with either RU24969, a 5-HT1B and 5-HT1A agonist or imipramine, a 5-HT uptake inhibitor. Pre- and postsynaptic 5-HT receptors were measured to compare the effect of direct or indirect stimulation of the 5-HT autoreceptor (5-HT1B receptor). The 5-HT transport protein (5-HT uptake site), labelled with [3H]paroxetine, was unaffected after treatment with either one of the drugs. The density of 5-HT2 receptors, labelled with [3H]ketanserin, we found increased after treatment with RU24969 (Bmax = 161 fmol/mg protein) and decreased after treatment with imipramine (Bmax = 109 fmol/mg protein) as compared with control rats (Bmax = 134 fmol/mg protein). The 5-HT1B receptor was found decreased both by the imipramine treatment (Bmax = 106 fmol/mg protein) and the treatment with RU24969 (Bmax = 105 fmol/mg protein), compared with control rats (Bmax = 130 fmol/mg protein). The 5-HT1A receptor was found to be decreased after treatment with RU24969 (control: Bmax = 62 fmol/mg protein; RU24969-treated: 49 fmol/mg protein), but unchanged after treatment with imipramine (Bmax = 58 fmol/mg protein). These results correspond to what could be expected, if the 5-HT1B receptor is the 5-HT autoreceptor.
Johanning
H
H
Department of Neuropsychiatry, Rigshospitalet, Copenhagen, Denmark.
Plenge
P
P
Mellerup
E
E
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D005260:Female; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects*; D014316:Tritium
D007211:Indoles; D011985:Receptors, Serotonin; D014316:Tritium; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D007099:Imipramine