ANXIOLYTIC ACTIVITY OF INTRAVENTRICULARLY ADMINISTERED ATRIAL-NATRIURETIC-PEPTIDE IN THE RAT

Rat atrial natriuretic peptide (ANP) was investigated for putative anx iolytic activity in rats, following intracerebroventricular (ICV) admi nistration ANP in doses of 200 and 500 ng/rat induced significant anxi olysis, comparable with that of lorazepam (0.5 mg/kg, IP) in a variety of anxiety models (open-field, elevated plus-maze, social interaction , and novelty-induced feeding suppression tests). Isatin, an endogenou s anxiogenic indole, shown to be an antagonist of ANP in vitro, signif icantly inhibited the anxiolytic effect of ANP in the elevated plus-ma ze test in subanxiogenic doses. The anxiolytic action of ANP was unaff ected by flumazenil, a benzodiazepine receptor antagonist. Conversely, the anxiolytic action of lorazepam teas antagonized by flumazenil but not by isatin. The data indicate that ANP may function as an endogeno us anxiomodulator, which may act in conjunction with isatin independen tly of benzodiazepine receptors. These results strengthen the evidence for links between physiological systems involved in anxiety and those in natriuresis.