Vasopressin antisense oligonucleotide induces temporary diabetes insipidus in rats

The purpose of this study was to downregulate the transcriptional message of arginine vasopressin (AVP) by antisense treatment. A complete phosphorothioate antisense oligodesoxynucleotide corresponding to the beginning of the coding region of rat AVP mRNA was constructed and injected into the lateral ventricle of rats. Within 3-6 h animals exhibited a temporary diabetes insipidus, which lasted up to 9 h. Accordingly, vasopressin immunoreactivity in the hypothalamic nuclei was reduced. Our results demonstrate that a specific and reversible inhibition of neuropeptide expression can be accomplished in the intact hypothalamo-neurohypophysial system by antisense treatment, thus providing a novel tool for studies on stimulus-secretion coupling in vivo.