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There have been many recent reports of receptor down-regulation in the brain by antisense oligodeoxynucleotides (ODNs) administered in vivo. However, the literature is inconsistent regarding the experimental criteria that are necessary or sufficient to demonstrate a true antisense effect. Here we review some of the critical conceptual and methodological issues. We highlight the problems of specificity and toxicity encountered in our attempts to down-regulate the 5-HT1A receptor using a phosphorothioate-modified ODN. We also present preliminary data suggestive of a decreased hippocampal 5-HT1AR expression induced by the antisense ODN, but it is a reduction which is of limited extent and which does not provide unequivocal evidence for an antisense-mediated effect. We conclude that antisense ODNs are not yet suitable as tools for routine in vivo neuropharmacological use, although they show considerable promise.

Type

Journal article

Journal

Neurochem Int

Publication Date

09/1997

Volume

31

Pages

349 - 362

Keywords

Analysis of Variance, Animals, Brain, Down-Regulation, Gene Expression, Injections, Intraventricular, Male, Oligonucleotides, Antisense, Radioligand Assay, Rats, Rats, Sprague-Dawley, Receptors, Serotonin