STRUCTURE-ACTIVITY STUDIES ON THE EFFECTS OF ATRIAL-NATRIURETIC-PEPTIDE, BRAIN NATRIURETIC PEPTIDE AND THEIR ANALOGS ON FEAR-MOTIVATED LEARNING-BEHAVIOR IN RATS

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.