3-bromo-7-nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs maternal aggression and citrulline immunoreactivity in prairie voles

Lactating female rodents are aggressive against intruders when they are rea ring and protecting pups. In prairie voles, Microtus ochrogaster, females e xhibit a dramatic increase in citrulline immunoreactivity (citrulline-IR) i n the paraventricular nucleus (PVN), but not in control regions of the brai n, in association with maternal aggression. Citrulline is an indirect indic ator of nitric oxide (NO) synthesis and it is possible that NO release in t he PVN is an important element in the control of maternal aggression in pra irie voles. In this study, we sought to examine the role of NO in maternal aggression by selectively inhibiting neuronal nitric oxide synthase (nNOS) in lactating prairie voles. Intraperitoneal injections of the nNOS inhibito r, 3-bromo-7-nitroindazole (3-Br-7NI) (20 mg/kg), three time per day over 4 days resulted in significant impairment of the expression of maternal aggr ession in terms of the average time in aggressive encounters, the average n umber of attacks, and the average latency to first attack. These behavioral deficiencies were observable beginning two days following the onset of dru g treatment. The average time spent sniffing the intruder was indistinguish able between the 3-Br-7NI- and oil-treated females. In 3-Br-7NI-treated rel ative to oil-treated females, the number of citrulline-positive cells was r educed by 70% in the PVN and by 50% in the anterior amygdaloid area, a cont rol region of the brain. Taken together, these results indicate that 3-Br-7 NI effectively inhibits maternal aggression and NO production in prairie vo les and suggest that the central release of NO may play an important role i n the production of maternal aggression in prairie voles. (C) 2000 Elsevier Science B.V. All rights reserved.