NMDA- and 6-OHDA-induced Lesions in the Nucleus Accumbens Differently Affect Maternal and Infanticidal Behavior in Pup-naïve Female and Male Mice.

Virgin and pups-naïve female and male adult mice display two opposite responses when they are exposed to pups for the first time. While females generally take care of the pups, males attack them. Since the nucleus accumbens (NA), and its dopaminergic modulation, is critical in integrating information and processing reward and aversion, we investigated if NMDA- and 6-OHDA-induced lesions, damaging mostly NA output and dopaminergic inputs respectively, affected female maternal behavior (MB) or male infanticidal behavior (IB) in mice. Our results revealed minor or no effects of both smaller and larger NMDA-induced lesions in MB and IB. On the other hand, while 6-OHDA-induced lesions in females reduced the incidence of full MB (12.5% 6-OHDA vs. 85.7% SHAM) increasing the latency to retrieve the pups, those lesions did not affect IB in males. There were no differences in locomotor and exploratory activity between the lesioned- and SHAM- females. Despite those lesions did not induce any major effect on IB, NMDA-lesioned males spent less time in the central area of an open field, while dopaminergic-lesioned males showed reduced number of rearing and peripheral crosses. The current study shows that an intact NA is not necessary for the expression of MB and IB. However, dopaminergic inputs to NA play different role in MB and IB. While damaging dopaminergic terminals into the NA did not affect IB, it clearly delayed the more flexible and rewarding expression of parental behavior.

Prefrontal cortex is associated with the rapid onset of parental behavior in inexperienced adult mice (C57BL/6).

There is significant variability in the immediate behavioral response displayed by inexperienced adult mice when exposed to pups for the first time. The aim of this study was to determine which brain regions were engaged (higher c-Fos-immunoreactivity, c-Fos-ir) when virgin females, that were exposed to pups for 15 or 60 min, displayed full parental behavior (FPB), partial parental behavior (PPB), or non-parental behavior (NPB), or virgin males displayed PPB or infanticidal behavior (IB). The number of c-Fos-ir neurons in the prelimbic cortex (PL) was higher in parental females than in the NPB group (after a 15-min exposure), and the group not exposed to pups (NE). C-Fos expression in the nucleus accumbens (NA) was increased in most groups of females exposed to pups compared to NE. Higher c-Fos-ir was also found in the shell subregion of the NA in infanticidal males, compared to males NE. The cortical (CoA) and medial (MA) amygdala also showed higher c-Fos-ir in parental females compared to NE animals. However, PPB and IB male groups also exhibited higher c-Fos-ir in the CoA and MA compared to the NE group. The expression of c-Fos in the different subregions of medial preoptic area and the ventromedial nucleus of the hypothalamus was not specifically associated with either parental or infanticidal behavior. No brain activation in males was specifically associated with infanticidal behavior. Our results suggest that 15 min of exposure to pups is enough to detect brain regions associated with parental behavior (PL) or pups processing (NA, MA, CoA) in mice. The PL might participate in the immediate onset of parental behavior in virgin females, coordinating and planning its rapid execution.