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DBA/2, CBA mice, and their F1 hybrids (first series) and 101/HY and C3H mice (second series) were injected as neonates (2-7 days of life) with Semax (sc., 7 microg per animal). Semax is a peptide analogue of ACHT4-10 fragment which is resistant to degradation. The common feature of remote effects of both Semax and saline injections was the set of changes in the open-field behavior in adult (2.5- to 3-month-old) animals as compared to intact mice. Unexpectedly, the neonatal saline injections induced many changes in adult behavior, part of these effects being genotype-dependent. The most conspicuous shifts (genotype-dependent increase or decline) in freezing, grooming and rearing scores were displayed by DBA/2 and C3H mice, whereas the hole-poke frequencies were significantly changed in CBA and C3H mice. Squares crossed in the center of arena and rearing number were significantly increased in saline group of DBA/2 mice, whereas in Semax-injected DBA/2 group they were approximately equal to the level of intact mice. This means that the remote effects of noxious stimulation (injections of saline) were in some ways "compensated" as the result of concomitant peptide effect. At the same time, the numbers of freezing and grooming episodes were also increased in these groups. Because exploratory behavior and manifestations of anxiety increased or decreased simultaneously, it proves to be difficult to ascribe these changes to behavioral modulation along the "novelty seeking--anxiety" axis. In mice of other genotypes, changes in the same indices of the open-field behavior were revealed, but these changes were different in their direction. It was suggested that the complex patterns of postnatal behavior was the result of neonatal injections modulating subsequent brain development.

We studied the effect of neonatal treatment with pharmacological preparations (Semax and buspiron) and solvents (distilled water and physiological saline) on the pain threshold in 3-4-month-old mice of 6 genotypes. Neonatal administration of the solvent (nociceptive stimulation) decreased pain thresholds in DBA/2, 101/HY, and RSB males, but not in female mice and animals of other strains. Neonatal administration of Semax significantly increased pain thresholds in adult DBA/2 and 101/HY males compared to those in animals neonatally treated with the solvent. Injection of buspiron in the neonatal period decreased pain thresholds in RLB males.

Neonatal injection of the ACTH4-10 fragment (5 micrograms daily for five days) caused genotype-dependent changes in concentrations of some monoaminergic neuromediators and their metabolites in hippocampus and brain stem of adult CBA and 101/HY mice. The catecholaminergic neurons increased in number in hypothalamic zona incerta of adult 101/HY mice. Neonatal injection of the peptide caused also genotype-dependent changes in the exploratory behavior of adult animals. Sound sensitivity was reduced in the 101/HY mice, whereas no sensitivity was revealed in both control and experimental groups of the CBA mice. The effects discovered were suggested to be caused by changes in neuronal differentiation.

We found that the administration of ACTH4-10 fragment to newborn mice of several strains (DBA/2, CBA, C57BL/6J, CBARb, and BLRb) for 5 days from the second day of life led to changes of several behavioral characteristics of adult animals. The effect of peptide administration on exploratory behavior of mice and on following the direction of stimulus movement are opposite to those induced by pain stimulation, i.e., administration of a solvent. The results are interpreted as a possible antistress effect of the peptide, which is realized during the period of neurodifferentiation. These data are discussed in terms of a possible effect of the used peptide on differentiation of the nervous system.