| Popis: |
The discovery of a novel serotonergic system within the mammary gland has led us to investigate central and peripheral serotonergic systems during lactation in an intact, non-depressed phenotype mouse model. During lactation we observed significant changes in both central and peripheral serotonergic physiologies. Platelet serotonin (5-HT) was elevated in lactating dams when compared to virgin animals. 5-HT immunostaining was significantly lower in the dorsal raphe of lactating mice than nulliparous mice. These findings are what led us to probe the serotonergic systems with a selective serotonin reuptake inhibitor (SSRI), citalopram. Lactating, nulliparous, and postpartum/non-lactating mice were all given a subchronic treatment regimen with SSRI and then subjected to behavioral tasks to assess mood-related behavior. Strikingly, only lactating dams responded to SSRI treatment with an improvement of mood-related behaviors. Locomotor and home-cage activity tasks indicated that these changes in behavior were specific to mood-related behaviors, and not due to an alteration of sensorimotor function. The novel findings from these studies are that lactating mice exhibit an elevated mood-related behavioral phenotype and respond to SSRI treatment that is ineffective in non-lactating mice. The current study shows that there is an interaction between lactation status and responsiveness to SSRIs, which has important implications for the treatment of postpartum depression (PPD).The immunostaining and behavioral results provide evidence of the potential enhancement of serotonergic activity into the projection fields of the brains of lactating mice. Using Palkovits micropunch technique we determined that there were changes in 5-HT and 5-HIAA activity within the posterior basolateral amygdala (PBLA), a brain region that may participate in mood regulation, of lactating mice. Furthermore, treatment with SSRI significantly reduced 5-HIAA content and increased 5-HT content within the PBLA of lactating dams. These results support the hypothesis that there is altered serotonergic activity within limbic projection fields. Again these changes were induced only within brains of lactating mice.The elevations in platelet 5-HT that were observed in lactating mice from our initial study led us to hypothesize that the upregulated serotonergic system within the mammary gland was responsible. Using a mammary specific knockout and overexpression mouse model of tryptophan hydroxylase, the rate limiting enzyme in 5-HT biosynthesis, we demonstrated that the mammary gland is the source of the elevated platelet 5-HT observed in lactating mice. Taken together these findings have significant clinical implications for the treatment of PPD. The clinical literature often does not address the breastfeeding (lactation) status of women when reporting or conducting studies in PPD. These data show that lactation is important and that there should be renewed interest in researching the interaction between breastfeeding and responsiveness to SSRI treatment during the postpartum period. |
