SEROTONIN RECEPTORS IN THE BRAIN OF RATS TREATED CHRONICALLY WITH IMIPRAMINE OR RU24969 - SUPPORT FOR THE 5-HT(1B) 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 [H-3]paroxetine, was unaffected after treatment with either one of the drugs. The density of 5-HT2 receptors, labelled with [H-3]ketanserin, we found increased after treatment with RU24969 (B(max) = 161 fmol/mg protein) and decreased after treatment with imipramine (B(max) = 109 fmol/mg protein) as compared with control rats (B(max) = 134 fmol/mg protein). The 5-HT1B receptor was found decreased both by the imipramine treatment (B(max) = 106 fmol/mg protein) and the treatment with RU24969 (B(max) = 105 fmol/mg protein), compared with control rats (B(max) = 130 fmol/mg protein). The 5-HT1A receptor was found to be decreased after treatment with RU24969 (control: B(max) = 62 fmol/mg protein; RU24969-treated: 49 fmol/mg protein), but unchanged after treatment with imipramine (B(max) = 58 fmol/mg protein). These results correspond to what could be expected, if the 5-HT1B receptor is the 5-HT autoreceptor.