Differential Effects of Neonatal Testosterone Treatment on Aggression in Two Selection Lines of Mice

Selection lines of mice, artificially selected for aggression based upon the attack latency score (ALS), were used. In order to determine the relative contribution of neonatal testosterone (T) in the development of aggression, we vary the plasma-T level in males of both selection lines on the day of birth. At 14 weeks the ALS was measured. Neonatal T treatment results in a reduction of aggression in the long attack latency (LAL) line, whereas aggressive behaviour of the short attack latency (SAL) line is not affected. Both selection lines show reduction in testicular weight, although the total amount of T-producing Leydig cells was not affected. Neonatal T may cause a permanent reduction in aggressive behaviour in the LAL line only, probably due to differential appearance of critical periods. It is suggested that the difference in aggressive behaviour between SAL and LAL selection lines is due to a prenatally determined difference in neonatal T sensitivity of the brain.

Enhanced sensitivity of postsynaptic serotonin-1A receptors in rats and mice with high trait aggression

Individual differences in aggressive behaviour have been linked to variability in central serotonergic activity, both in humans and animals. A previous experiment in mice, selectively bred for high or low levels of aggression, showed an up-regulation of postsynaptic serotonin-1A (5-HT1A) receptors, both in receptor binding and in mRNA levels, in the aggressive line. The aim of this experiment was to study whether similar differences in 5-HT1A receptors exist in individuals from a random-bred rat strain, varying in aggressiveness. In addition, because little is known about the functional consequences of these receptor differences, a response mediated via postsynaptic 5-HT1A receptors (i.e., hypothermia) was studied both in the selection lines of mice and in the randomly bred rats. The difference in receptor binding, as demonstrated in mice previously, could not be shown in rats. However, both in rats and mice, the hypothermic response to the 5-HT1A agonist alnespirone was larger in aggressive individuals. So, in the rat strain as well as in the mouse lines, there is, to a greater or lesser extent, an enhanced sensitivity of postsynaptic 5-HT1A receptors in aggressive individuals. This could be a compensatory up-regulation induced by a lower basal 5-HT neurotransmission, which is in agreement with the serotonin deficiency hypothesis of aggression.

Differential testosterone secretory capacity of the testes of aggressive and nonaggressive house mice during ontogeny

In this study, testosterone secretory capacity of testicular Leydig cells during ontogeny was determined in males of an aggressive and a nonaggressive genetic selection line of wild house mice. Neonates, 23-day-old prepubertals, and adult male mice were studied. A morphometric method was used to quantify 3-beta-hydroxy steroid dehydrogenase (3-beta-HSD)-stained Leydig cells in testicular sections to determine testosterone secretory capacity. We consider this parameter to reflect circulating testosterone in the plasma. The results of this study show that the testosterone secretory capacity of Leydig cells in the testis changes differentially during development in males of the aggressive and nonaggressive selection lines. This capacity is highest in the aggressive selection line males at adulthood and at the prepubertal age of 23 days. Surprisingly, at birth, the highest T-secretory capacity was observed in the males of the nonaggressive selection line. The significance of an interaction between genetic factors and differences in perinatal testosterone for the individual variation in adult aggressive behavior is discussed.</p

Differential Perinatal Testosterone Secretory Capacity of Wild House Mice Testes Is Related to Aggressiveness in Adulthood

Testosterone secretory capacity of testicular Leydig cells was determined in fetal males of an aggressive and a nonaggressive genetic selection line of wild house mice. They were studied at Days 15-18 of gestation and on the first day after birth. A previously described morphometric method was used to quantify 3β-hydroxy steroid dehydrogenase (3β-HSD)-stained Leydig cells in testicular sections to determine testosterone secretory capacity, which may be considered to reflect circulating plasma testosterone in the fetus. The results of this study show that the testosterone secretory capacity of Leydig cells in the testis changes differentially during intrauterine development in males of the aggressive and nonaggressive selection lines. The peak secretory capacity is reached at Day 17 of gestation for the males of the aggressive selection line, while the peak for the nonaggressive males is reached on the first neonatal day. The larger anogenital distance observed in aggressive males suggests a higher prenatal testosterone level in these males. The importance of the difference in timing of the perinatal 3β-HSD peak top individual variation in adult aggressive behavior is discussed.

Genetic Differences in Female House Mice in Aggressive Response to Sex Steroid Hormone Treatment

Male mice, genetically selected for aggression, characterized by short attack latency (SAL) or long attack latency (LAL), differ on several testosterone (T)-related parameters during ontogeny and adult age. The variation in aggressive behavior at adult age may be due to differences in degree of androgenization prenatally. When exposed to T at prenatal, neonatal, and/or adult age, nonlactating females also display intraspecific fighting behavior. In the present study, we investigated in females of the SAL and LAL selection lines, whether the differentiation of aggression involves processes similar to ones seen in males. Therefore, we injected females with testosterone propionate (TP) or vehicle on the day of birth, treated them after ovariectomy at adult age with T, estradiol (E), or vehicle, and tested their aggressive response. We found that neonatally vehicle-treated SAL females show a higher aggressive response to chronic T treatment at adult age than LAL females receiving the same treatment. Females of both selection lines treated with vehicle or E as adults were not aggressive. Neonatal TP treatment did not influence the adult T sensitivity and difference between selection lines in response to T at adult age. However, neonatally TP-treated SAL females showed aggressive behavior when treated with E at adult age, whereas LAL females failed to do so. These results suggest a genetic difference in susceptibility to T and E, which plays a major role prenatally, in organizing the development of sex steroid-dependent neural systems.