Reproductive and stress axis hormones have profound influences on social behaviour, and dramatic changes in the hormonal milieu within the brain following parturition may underlie emotional instability at this time. Female rats are not normally aggressive, but post-partum they become fiercely aggressive towards other rats. Aggressive behaviour is part of the complex suite of maternal behaviour that ensures protection of the offspring, for example, by preventing an intruder from attacking or even killing the pups . Thus the lactating rat is a useful model to study the neuroendocrine mechanisms that control this behavioural switch. The central oxytocin and vasopressin systems are putative modulators of maternal aggression since they undergo regulatory changes that are temporally synchronised with the expression of maternal behaviour. As the regulation of these neuroendocrine systems peripartum may be relevant to direct central effects of these neuropeptides on behaviour, we investigated receptor expression in the brain from pregnancy and through to lactation. Quantitative in situ hybridisation for oxytocin receptor and vasopressin receptor mRNA expression has revealed dynamic changes around the time of birth. Changes in receptor expression distribution and density patterns in hypothalamic and limbic brain areas point to the crucial role neurohypophyseal hormones play in orchestrating parturition, but importantly these changes may also contribute to observed maternal aggression levels. In a recent study we sought to identify the neural basis of maternal aggression by using immunocytochemistry for the expression of the immediate early gene Fos protein (an indicator of neuronal activation). In a resident intruder paradigm, Fos expression was significantly increased in brain regions such as the olfactory bulbs, lateral septal nucleus, bed nucleus of the stria terminalis (BnST), supraoptic nucleus (SON), paraventricular nucleus (PVN), central amygdala (CeA) and ventromedial hypothalamus of aggressive lactating rats compared to controls. Activated cells in the PVN and SON, were additionally double labelled for vasopressin or oxytocin. Further double labelling studies indicate that vasopressin receptor (V1a and V1b) expressing neurones and corticotropin releasing factor (CRF) cell populations in the CeA and BnST are also activated. It is unclear how central CRF relates to maternal aggression, but CRF neurone activation in the CeA and BnST may serve as a response to fear particularly since CRF has putatively anxiogenic properties [2, 3]. In a separate study using resident intruder tests on lactating rat dams selectively bred for extremes in emotionality, i.e. for high (HAB) and low (LAB) anxiety-related behaviour  we have shown that innate anxiety levels of the dam persist during lactation and underlie the intensity of maternal aggressive behaviour . HAB dams demonstrate overprotective behaviour by spending significantly more time in direct pup contact and are more aggressive during the resident intruder paradigm compared to LAB dams. To test the hypothesis that intracerebral oxytocin and vasopressin release patterns are crucially involved in determining levels of maternal aggression we experimentally manipulated brain oxytocin and vasopressin systems. Oxytocin and vasopressin release, as measured by intracerebral microdialysis, increased within the CeA of HAB but not LAB rats during the resident intruder paradigm. Local oxytocin blockade by bilateral retrodialysis of an oxytocin receptor antagonist into either the PVN or the CeA of HAB dams resulted in reduced maternal aggression, whereas the infusion of oxytocin into the PVN or vasopressin into the CeA of LAB dams tended to increase their aggression. These findings lead to the assumption that high local oxytocin levels transiently reduce anxiety to enable the expression of aggressive behaviour towards the potentially dangerous intruder; however this hypothesis remains to be tested. Involvement of the vasopressin system in male rodent aggression is increasingly understood however the role of vasopressin in maternal aggression warrants further investigation. In summary, we have identified several populations of neurones, including those in the limbic system that are involved in maternal aggression. Moreover the present results provide evidence that maternal aggressive behaviour in the rat is dependent on inborn emotionality and its regulation involves central oxytocin, vasopressin and CRF systems. Acknowledgements: Acknowledgements: This work was supported by the BBSRC. Reference 1 : Gammie SC (2005) Behav Cogn Neurosci Rev 4: 119-135. Reference 2 : Jasnow AM et al (2006) Horm Behav 49: 197-205. Reference 3 : D'Anna KL et al (2005) Behav Neurosci 119: 1061-1071. Reference 4 : Landgraf R & Wigger A (2003) Stress 6: 111-119. Reference 5 : Bosch OJ et al (2005) J Neurosci 25: 6807-6815.
|Journal||Proceedings of The Physiological Society|
|Publication status||Published - 2007|