The efficiency of antisense approaches to produce a selective regional inhibition of the expression of brain 5-HT1A receptors was tested in the rat. In vivo ICV injections of modified antisense oligodesoxynucleotides yielded at most an 18% specific decrease in 5-HT1A receptor expression in the hippocampus only, as measured by [3H]8-OH-DPAT autoradiographic labeling. In vitro, when 5-HT1A receptors were transiently expressed in LLC-PK1 cells, co-transfection with antisense RNA encoding plasmids resulted in a marked reduction (50-70%) in the density of 5-HT1A binding sites. In vivo stereotaxic injections of the same constructs into the hippocampus, but not in the raphe, which contains 5-HT1A autoreceptors, were shown to produce a approximately 20% reduction in local 5-HT1A receptor density. These data show that antisense strategies could be used to inhibit 5-HT1A receptors expression in the rat hippocampus, but with a limited efficacy.
