Limited inhibition of 5-HT1A receptor expression in the rat brain by antisense RNA and oligodesoxynucleotides

The efficiency of antisense approaches to produce a selective regional inhi bition of the expression of brain 5-HT1A receptors was tested in the rat. I n vivo ICV injections of modified antisense oligodesoxynucleotides yielded at most an 18% specific decrease in 5-HT1A receptor expression in the hippo campus only, as measured by [H-3]8-OH-DPAT autoradiographic labeling. In vi tro, when 5-HT1A receptors were transiently expressed in LLC-PK1 cells, co- transfection with antisense RNA encoding plasmids resulted in a marked redu ction (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 raph e, which contains 5-HT1A autoreceptors, were shown to produce a similar to 20% reduction in local 5-HT1A receptor density. These data show that antise nse strategies could be used to inhibit 5-HT1A receptors expression in the rat hippocampus, but with a limited efficacy. (C) 1999 Elsevier Science ire land Ltd. All rights reserved.