Dynamic region-dependent changes in oxytocin receptor expression in the rat brain at parturition

Simone Meddle, Valerie Bishop, Effimia Gkoumassi, Fred van Leeuwen, Alison Douglas

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Abstract

Centrally oxytocin plays a pivotal role in parturition, facilitating its own release centrally and peripherally and effecting maternal behaviour. Since quality of social and maternal behaviours depends upon pattern of oxytocin receptor (OTR) distribution1, we investigated the expression and activation of oxytocin-receptive neurones perinatally. OTR mRNA expression was quantified in dioestrus virgin, 21 and 22 day pregnant (pre-parturition), parturient and postpartum (<12h) rats (n=10,8,7,9,9, respectively) by in situ hybridisation using a 35S-labelled riboprobe; data are mean±S.E.M and each brain region was analysed by 1 way ANOVA and posthoc tests. The highest OTR mRNA expression was in the supraoptic (SON) and paraventricular (PVN) nuclei. Pre-parturition OTR mRNA expression was increased only in the SON compared to virgins (43333±3889 vs. 30556±1111 pixels per cell, p<0.01), suggesting oxytocin control of the input from the uterus during labour. During parturition peak OTR mRNA expression was observed in the SON, A2/C2 and A1/C1 brainstem regions, medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST), olfactory bulbs and medial amygdala (increase above virgin=45,82,68,119,55,79 & 46% respectively; all p<0.05). Parturition increased OTR mRNA expression vs. pre-parturition only in the olfactory bulb and amygdala (increase=34 & 21% respectively, p<0.05), reflecting a rapid response to birth stimuli. Within 12h postpartum, OTR mRNA expression decreased and was not significantly different from virgins in all regions. OTR mRNA expression in the PVN and lateral septum did not alter perinatally. Further virgin, 21day pregnant and parturient (n=6,6,8, respectively) rats were perfused-fixed and their brains processed by double immunocytochemistry for Fos and OTR. The number of Fos-positive OTR neurones was significantly increased during parturition but not before, especially in the SON (63.5±8.8 vs virgin 9.8±3.2 cells per region); for A2/C2 and A1/C1 brainstem regions, MPOA, BNST and medial amygdala Fos-positive OTR neurones per region were 3.3,12.0,11.4,15.3 & >22 fold above virgins, respectively (p<0.05). Fos and OTR co-expression in the parvocellular PVN and lateral septum was not significantly changed during parturition. So, selected OTR expressing neurones in selected brain regions are activated during birth and play a role in mediating behaviour. Thus, as in the uterus, there are dynamic changes in oxytocin receptor expressing cells at parturition. Responses are region-dependent, altering the pattern of oxytocin receptor distribution in the brain perinatally. Increased expression and activation of OTR neurones reflects the crucial role they play in orchestrating birth and maternal behaviour; altered patterns may shape quality of behaviour. Acknowledgements: We thank The Wellcome Trust & BBSRC for financial support.Reference 1 : Olazabal DE and Young LJ. (2006) Horm Behav 49:681-7.
Original languageEnglish
JournalProceedings of The Physiological Society
Volume6
Issue numberPC10
Publication statusPublished - 2007

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