CENTRAL SEROTONIN-1A RECEPTORS - RESPECTIVE DISTRIBUTIONS OF ENCODING MESSENGER-RNA, RECEPTOR PROTEIN AND BINDING-SITES BY INSITU HYBRIDIZATION HISTOCHEMISTRY, RADIOIMMUNOHISTOCHEMISTRY AND AUTORADIOGRAPHIC MAPPING IN THE RAT-BRAIN

The regional distribution of the mRNA encoding the 5-HT1A serotonin receptor (whose selective agonists are potential anxiolytic and antidepressant drugs) was investigated in rat brain sections by in situ hybridization histochemistry using two sets of [P-32]labelled nucleoprobes, a riboprobe of 156 bases and oligoprobes of 30 bases corresponding to highly selective portions within the third intracellular loop and the N terminus domain of the amino acid sequence. These probes allowed the visualization of the 5-HT1A mRNA mainly in the limbic regions: dentate gyrus and area CA1 of the hippocampus, amygdala, entorhinal cortex, lateral septum and the dorsal raphe nucleus. These structures were also those which could be labelled by the specific 5-HT1A radioligand [I-125]BH-8-MeO-N-PAT and antibodies raised against a synthetic 26 amino acid peptide whose sequence was taken from the most selective portion of the rat 5-HT1A receptor protein. These data suggest that the 5-HT1A receptors are not transported to a long distance from their site of synthesis, as it has been already reported for the somato-dendritic 5-HT1A autoreceptors in the dorsal raphe nucleus. Combined autoradiographic quantification of the 5-HT1A binding sites (labelled by a selective radioligand such as [I-125]BH-8-MeO-N-PAT), the 5-HT1A receptor binding subunit (by radioimmunohistochemistry) and the 5-HT1A mRNA on adjacent brain sections should be a relevant approach for assessing the molecular mechanisms responsible for the functional alterations of these receptors under various pathological and pharmacological conditions.