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Partial amnesia was induced in rats by electroconvulsive shock (ECS) immediately after passive avoidance learning. This partial amnesia could be prevented by administering porcine brain natriuretic peptide-32 (pBNP-32) into the lateral brain ventricle. The effects of pretreatment with different receptor blockers (haloperidol, atropine, phenoxybenzamine, propranolol, naloxone, bicuculline and methysergide) on the pBNP-32-induced antiamnesia were investigated. In the doses selected, the blockers had no influence on the ECS-induced amnesia. Haloperidol, atropine, phenoxybenzamine and propranolol blocked the antiamnesic action of the peptide, while naloxone, bicuculline and methysergide were ineffective. These results suggest that pBNP-32 may influence learning processes and that the antiamnesic action of this peptide is mediated by dopaminergic, cholinergic α- and β-adrenergic mediator systems.

The effects of two doses of rat atrial natriuretic peptide (TANP-1-28), 200 and 500 ng, on 6-day acquisition and extinction of food-reinforced conditional learning (conditional stimulus: light) were studied in rats following administration into the lateral cerebroventricle. With the higher dose, there was a tendency for facilitated acquisition and significantly delayed extinction of the positively reinforced learning task. In order to clarify whether the effect of the peptide is obtained through the involvement of neurotransmitters, the experimental animals were pretreated with different receptor blockers in selected doses that did not influence the behavioral test. Haloperidol, atropine, phenoxybenzamine, and propranolol blocked the action of ANP on extinction of the food-reinforced conditioning, whereas naloxone, bicuculline, and methysergide were ineffective. The results suggest that ANP might be considered a modulating agent in a positively reinforced conditional learning task, and that its action might involve dopaminergic, cholinergic, and alpha- and beta-adrenergic mechanisms.

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 phenoxy-benzamine/propranolol, naloxone, bicuculline and methysergide were ineffective. The data suggest that ANP delays the extinction of active avoidance behavior, and the 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.

The effects of rat atrial natriuretic peptide (ANP 1–28) on passive avoidance behaviour were tested following its administration into the lateral brain ventricle in rats. Different doses of ANP 1–28 were administered immediately after the learning trial of passive avoidance behaviour and the effects on the consolidation of learning were tested 24 h later. ANP 1–28, in doses in the range 50–2000 ng/rat, caused a dose-dependent increase in passive avoidance latency. Selected doses (100, 200 and 500 ng/animal) were given 30 min before the learning trial. These doses lengthened the passive avoidance latency in a dose-dependent manner. When the peptide was given 30 min before the retention trial, there was no significant alteration in passive avoidance response. The data suggest that ANP 1–28 is able to facilitate the learning and consolidation of fear-motivated passive avoidance behaviour.

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.

Previous studies have demonstrated that rANP(1–28) administered into the lateral cerebroventricle facilitates consolidation of the passive avoidance response and delays extinction of the active avoidance response in fear-motivated learning in rats. To study the role of endogenous ANP in the same learning processes, the effects of different dilutions of ANP antiserum were investigated following their intracerebroventricular administration to rats. At dilutions of 1:40 and 1:60, the ANP antiserum attenuated consolidation of the passive avoidance response. It also facilitated extinction of the active avoidance response at a dilution of 1:2. The results suggest that endogenous ANP might be considered a modulating agent in the brain, and is involved in the learning processes and memory trace formation, since intracerebroventricularly administered antiserum against ANP attenuated fear-motivated learning behavior in the experimental animals.

The effects of certain neuropeptides on electroconvulsive (ECS) shock-induced amnesia were studied in rats. The ECS was applied immediately after the learning a one-trial passive avoidance paradigm. The peptides--rat atrial natriuretic peptide (rANP 1-28, ANP), porcine brain natriuretic peptide (pBNP 1-32, BNP), rat calcitonin gene-related peptide (CGRP) and bombesin--were injected into the lateral brain ventricle 30 min after the ECS. In order to study the possible role of neurotransmitters in mediating the action of the peptides on amnesia, the animals were treated immediately after the ECS with, doses which themselves did not modify either the learning itself or the amnesic action of the ECS. All the above peptides attenuated the ECS-induced amnesia, but the transmitters involved in these actions differed. The anticonvulsive action of ANP was prevented by haloperidol (10 micrograms/kg i. p.), propranolol (10 mg/kg i. p.) and atropine (2 mg/kg i. p.). Phenoxybenzamine (2.0 mg/kg i. p.), bicuculline (1 mg/kg i. p.), methysergide (5 mg/kg i. p.) and naloxone (0.3 mg/kg i. p.) had no effect. Besides alpha-adrenergic and cholinergic receptor blockers the beta-adrenergic blocker propranolol was also effective in preventing the antiamnesic action of the BNP. As concerns the action of bombesin, only haloperidol was effective. Alpha- and beta-adrenergic and cholinergic receptor blockers and opiates are involved in the antiamnesic properties of CGRP. The results showed that, despite the fact that the studied, peptides attenuated the ECS-induced amnesia, different transmitters are involved in their action.

The effect of rat atrial natriuretic peptide (ANP 1–28 ) on the pargyline-DOPA potentiation test was studied following its administration into the lateral brain ventricle in mice. Thirty minutes after pargyline pretreatment, three doses of ANP (200, 500, or 1,000 ng/mouse) were administered simultaneously with DOPA and animals were then observed for 2 h. ANP in doses of 500 and 1,000 ng markedly enhanced the effect of DOPA. The maximum intensity of the effect was registered 30–45 min following administration of the peptide. The data suggest that ANP might be regarded as a dopaminergic-modulating agent in the CNS.

In previous experiments, it was observed that rat atrial natriuretic peptide-(1–28) (ANP-(1–28)) participated in fear-induced learning and memory processes via dopaminergic and cholinergic mediation. Since cage-climbinh behavior is described as a simple test for studying dopaminergic activity in the central nervous system, a systematic study was carried out with ANP-(1–28) in order to confirm or to exclude the possible involvement of dopamine in the ANP-induced action in the brain. The present study demonstrates that ANP-(1–28) facilitated cage-climbing behavior in mice in a dose-dependent manner. When combined with apomorphine, the peptide potentiated the effect of the dopamine agonist. The effect of ANP-(1–28) in combination with apomorphine could be antagonized by a selected dose of haloperidol. These data suggest that ANP might be regarded as a dopamine agonist-modulating agent and that a dopaminergic mechanism is a possible mode of action of ANP in the fear-induced learning studied earlier.

In previous experiments, it was shown that rat atrial natriuretic peptide (rANP 1−28 ) 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.