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Our previous studies have demonstrated that rat atrial natriuretic peptide (rANP 1-28) and porcine brain natriuretic peptide (pBNP 1-32) administered into the lateral brain facilitate the consolidation of a passive avoidance response and delay the extinction of an active avoidance response in fear-motivated learning in rats. To study the structure-activity relationships in the same learning processes, the effects of several fragments related to ANP and BNP were investigated following their intracerebroventricular administration to rats. The following peptides were studied: rANP 1-28, rANP 5-28, rANP 5-27, rANP 7-23 (ring), rANP 17-23, hANP 10-28, hANP 15-28, hANP 20-28, hANP 1-28, pBNP 1-32 and pBNP 7-32. The peptides were used in equimolar concentration. Two of the peptides studied, ANP 20-28 and ANP 17-23, were ineffective on the extinction of active avoidance behavior and on the consolidation of passive avoidance learning. They exhibited similar actions. The results showed that small fragments of ANP and BNP can carry the biological activity of ANP and BNP on the central nervous system (CNS). It is likely that the biological active center for ANP lies between amino acids 15 and 23 and it is suspected that the ring structure is not absolutely important for the CNS activity.

The effects of several doses of porcine brain natriuretic peptide-32 (pBNP-32) administered into the lateral brain ventricle were tested as regards the consolidation of passive avoidance learning in rats. The peptide was found to increase the passive avoidance latency in a dose-dependent manner. In order to clarify which transmitter systems might be involved in the action of pBNP-32, the experimental animals were pretreated with different receptor blockers in selected doses which did not influence the behavioral paradigm. Four of the receptor blockers (haloperidol, atropine, phenoxybenzamine and propranolol) effectively blocked the action of the peptide on the consolidation of passive avoidance learning. The other three (naloxone, bicuculline and methysergide) were ineffective. The results suggest that dopaminergic, cholinergic and alpha- and beta-adrenergic mediations might be involved in the effects of pBNP-32 on the consolidation of passive avoidance learning in rats.

In the present study, four doses (50, 100, 200 or 500 ng per animal) of rat atrial natriuretic peptide (rANP1-28) were tested on the open-field activity of rats following i.c.v. application of the peptide. ANP in doses of 200 ng or 500 ng/rat significantly increased the ambulation activity 15 min after the treatment. However, the effect was transitory; 30 min after application it was no longer observed. When the experimental animals were pretreated with different receptor blockers in doses which per se could not affect the behavioral paradigm, the effect of ANP was completely blocked by haloperidol (a dopaminergic blocking agent), phenoxybenzamine (an alpha-adrenergic blocker) and propranolol (a beta-adrenergic blocker). Atropine, naloxone, bicuculline and methysergide were ineffective. These results suggest that dopaminergic and adrenergic transmitter systems are involved in the ANP-induced locomotor activity of rats.

In previous experiments, it was shown that rat atrial natriuretic peptide (rANP1-28) is able to increase the passive avoidance latency in a dose-dependent manner in the learning and consolidation phase (3). In order to clarify whether ANP has a direct action on this behavioral paradigm, or whether the action is mediated by neurotransmitters, rats were pretreated with different receptor blockers. The selected doses of the different receptor blockers could themselves not influence the behavioral paradigms. Haloperidol or atropine blocked the action of ANP on the consolidation of the passive avoidance response. Phenoxybenzamine, propranolol, methysergide, bicuculline and naloxone were ineffective. The data suggest that dopaminergic and cholinergic mediations are involved in the action of ANP on the passive avoidance response.

Different doses of rat atrial natriuretic peptide (rANP1-28) were tested as regards the extinction of active avoidance behavior following its injection into the lateral brain ventricle in rats. ANP delayed extinction of the active avoidance reflex in a dose-dependent manner. When the animals were pretreated with different receptor blockers in doses which themselves had no action on the extinction of active avoidance behavior, the action of ANP on this paradigm was completely blocked by haloperidol and atropine, whereas phenoxybenzamine/propranolol, naloxone, bicuculline and methysergide were ineffective. The data suggest that ANP delays the extinction of active avoidance behavior, and that cholinergic and dopaminergic transmitter systems might be involved in this action.

Electroconvulsive shock (ECS) applied immediately after passive avoidance learning in rats caused partial amnesia. This could be prevented by administering r-ANP into the lateral brain ventricle. The effects of pre-treatment with different receptor blockers: (haloperidol, atropine, phenoxybenzamine, propranolol, naloxone, bicuculline and methysergide) on the ANP-induced antiamnesia were investigated. The receptor blockers per se in the doses selected had no influence on the ECS-induced amnesia. Haloperidol, atropine and propranolol blocked the antiamnestic action of the peptide, while phenoxybenzamine, naloxone, bicuculline and methysergide were ineffective. The results confirm our previous observations that ANP might play a role in learning and memory processes and also suggest that the antiamnestic action of the peptide is mediated by dopaminergic, cholinergic and beta-adrenergic mediator systems.