Experiments were performed to evaluate the role of central oxytocin (OT) in the inhibition of salt intake produced by sinoartic denervation (SAD). The effect of OT antisense treatment on 24 h intake of 2% NaCl in SAD and sham-operated (SO) rats was determined. PVN injection of unmodified antisense oligodeoxynucleotides (ODNs) to OT mRNA decreased intake of 2% NaCl in SAD, but not SO rats. Salt consumption was 22 +/- 4 ml after the injection of control ODN as compared to 8 +/- 4 ml after the OT antisense injection (P < 0.05). SAD animals also demonstrated an increased plasma OT response to salt loading, an elevation from 3.2 +/- 0.7 to 6.9 +/- 0.8 pg/ml. In contrast, salt ingestion produced no significant change in plasma OT in the SO group. The increased endocrine response in the SADs occurred even though salt intake was lower in this group. There were no group differences in plasma electrolytes or posterior pituitary OT content. Results show that OT antisense specifically inhibits salt intake in the denervated rat, suggesting that the central oxytocinergic axis stimulates sodium drive in this experimental model.