Serotonin Receptors in the Brain of Rats Treated Chronically with Imipramine or RU24969: Support for the 5‐HT1BReceptor Being a 5‐HT Autoreceptor

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Abstract
Rats were treated by intraperitoneal injection for four weeks with either RU24969, a 5‐HT1Band 5‐HT1Aagonist 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‐HT1Breceptor). 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‐HT1Breceptor 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‐HT1Areceptor 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‐HT1Breceptor is the 5‐HT autoreceptor.