Anxiolytic Activity of Intraventricularly Administered Atrial Natriuretic Peptide in the Rat

Rat atrial natriuretic peptide (ANP) was investigated for putative anxiolytic activity in rats, following intracerebroventricular (ICV) administration. ANP in doses of 200 and 500 ng/rat induced significant anxiolysis, comparable with that of lorazepam (0.5 mg/kg, i.p.) in a variety of anxiety models (open-field, elevated plus-maze, social interaction, and novelty-induced feeding suppression tests). Isatin, an endogenous anxiogenic indole, shown to be an antagonist of ANP in vitro, significantly inhibited the anxiolytic effect of ANP in the elevated plus-maze test in subanxiogenic doses. The anxiolytic action of ANP was unaffected by flumazenil, a benzodiazepine receptor antagonist. Conversely, the anxiolytic action of lorazepam was antagonized by flumazenil but not by isatin. The data indicate that ANP may function as an endogenous anxiomodulator, which may act in conjunction with isatin independently of benzodiazepine receptors. These results strengthen the evidence for links between physiological systems involved in anxiety and those in natriuresis.