Josje C. Compaan

Differential Lateral Septal Vasopressin Innervation in Aggressive and Nonaggressive Male Mice

The vasopressinergic (VP) projection from the bed nucleus of the stria terminalis (BNST) to the lateral septum (LS) is sexually dimorphic and dependent of androgens at adult and neonatal age. We studied the relation between testosterone (T) and VP in male mice, which were genetically selected for their differences in aggression level. Aggressive males, characterized by a short attack latency (SAL), have a higher production capacity of T at adult age compared to males with a long attack latency (LAL). Neonatally, however, a higher T production occurs in the nonaggressive LAL males than in SAL males. In the present study we showed a more dense VP-immunoreactive (VP-ir) innervation in the LS and a higher VP-ir neuron density in the BNST of LAL males as compared to SAL males. The described differences may be the consequence of a differential neonatal androgen effect on the organization of the forebrain vasopressinergic network.

DIFFERENCES IN THE NUMBER OF ARGININE-VASOPRESSIN-IMMUNOREACTIVE NEURONS EXIST IN THE SUPRACHIASMATIC NUCLEI OF HOUSE MICE SELECTED FOR DIFFERENCES IN NEST-BUILDING BEHAVIOR

Arginine-vasopressin (AVP) is a homeostatic modulator of body temperature during fever and may also be involved in normal body temperature control. In the present study the hypothalamus of mice bi-directionally selected for thermoregulatory nest-building behavior was immunocytochemically labeled for AVP. The low-selected mice had a 1.5-fold higher number of AVP-immunoreactive neurons in the suprachiasmatic nuclei (SCN) compared to the unselected control and the high-selected mice. No differences between the selected lines could be detected in the number of AVP-immunoreactive neurons in the paraventricular nuclei (PVN). The neuroanatomical data suggest a possible role of AVP in the SCN and control of thermoregulatory nest-building behavior. Our selected mice may prove to be a model system to study the role of AVP in the SCN.

Long-term effects of cholinergic basal forebrain lesions on neuropeptide Y and somatostatin immunoreactivity in rat neocortex

The effect of cholinergic basal forebrain lesions on immunoreactivity to somatostatin (SOM-i) and neuropeptide-Y (NPY-i) was investigated in the rat parietal cortex, 16-18 months after multiple bilateral ibotenic acid injections in the nucleus basalis complex. As a result of the lesion, the cholinergic fiber density in the cortex decreased by 66% with a concurrent increase in SOM-i fibers by more than 50% and a 124% increase in NPY-i fiber innervation. The neuropeptidergic sprouting response on cholinergic denervation does not match the concurrent cholinergic and peptidergic decline in Alzheimers disease and as such does not support the cholinergic lesion alone as an animal model for this neurodegenerative disorder.

Brain aromatase activity and plasma testosterone levels are elevated in aggressive male mice during early ontogeny

Testosterone (T) and estradiol (E2) are involved in intraspecific aggressive behavior. Both steroids exert their effects on behaviour via the hypothalamus and the amygdala (Am) of the central nervous system (CNS). In these brain areas T is converted to E2, by the enzyme aromatase. Both the levels of brain aromatase activity (AA) and the effects of T and E2 on aggressive behavior in adulthood depend on steroidal organization of the CNS during ontogeny. In this study we measured plasma T and in vitro brain AA of males fetuses and neonates derived from two strains of wild house mice, which had been genetically selected for aggression, based upon attack latency. There were no differences in preoptic area (POA) AA levels between selection lines on either embryonic day (E) 17 or 18, or the day after birth (day 1). In the non-aggressive long attack latency (LAL) males the POA AA increases with age, i.e. was higher on E18 than on E17, which is correlated with brain weight (BrW). This was in contrast to aggressive short attack latency (SAL) fetuses, which only showed a slight, but not significant differences between embryonic days or a correlation with BrW. Neonatally, the POA AA of LAL males tended to decrease in contrast to SAL males. However, SAL neonates had a higher AA in the amygdala (Am) than LAL neonates, whereas no differences exist in the anterior hypothalamus. Thus, a differential brain AA distribution exists in SAL and LAL pups.(ABSTRACT TRUNCATED AT 250 WORDS)

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 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.

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.