Acute, sequence-specific effects of oxytocin and vasopressin antisense oligonucleotides on neuronal responses

Antisense oligodeoxynucleotides (antisense) are short length single strands of DNA with base sequences complementary to a length of messenger RNA of a specific gene. They can be taken up by neurons and hybridize with a complementary messenger RNA to selectively interrupt the expression of a particular gene. We now describe neuropeptide-specific, short-latency (within 2-6 h) effects of antisense infused into the supraoptic nucleus on the responses of rat neurohypophysical neurons, in vivo, to various stimuli. Oxytocin antisense specifically (i) reduced the electrophysiological responses of putative oxytocin, but not vasopressin neurons, (ii) inhibited cholecystokinin-induced and electrically stimulated release of oxytocin from the neurohypophysis, and (iii) reversibly abolished cholecystokinin-induced expression of Fos within the supraoptic nucleus. Vasopressin antisense reduced the excitatory responses of vasopressin neurons, but not of oxytocin neurons. As neuropeptide content within the supraoptic nucleus and neurohypophysis remains unaltered at this time, antisense may induce anticipatory, feed-forward alterations in electrical activity in addition to any possible effects on peptide synthesis.