Biology subjects

Albers, H. E.

Publications and source records attributed to Albers, H. E..

2 recordsLinked to original sources

bioRxiv2020

Estrogen withdrawal alters oxytocin signaling in the paraventricular hypothalamus and dorsal raphe nucleus to increase postpartum anxiety

BackgroundEstrogen increases dramatically during pregnancy, but quickly drops below pre-pregnancy levels at birth and remains suppressed during the postpartum period. Clinical and rodent work suggests that this postpartum drop in estrogen results in an "estrogen withdrawal" state that is related to changes in affect, mood, and behavior. Most studies examining the effect of estrogen withdrawal on the brain have focused solely on the hippocampus. MethodsWe used a hormone-simulated pseudopregnancy model in Syrian hamsters, a first for this species. Ovariectomized females were given daily injections to approximate hormone levels during gestation and then withdrawn from estrogen to simulate postpartum estrogen withdrawal. Subjects were tested for behavioral assays of anxiety and anhedonia during estrogen withdrawal. Following sacrifice, neuroplasticity in oxytocin-producing neurons in the paraventricular nucleus of the hypothalamus (PVH) and its efferent targets was measured. ResultsEstrogen-withdrawn females had increased anxiety-like behaviors in the elevated plus and open field, but did not differ from controls in sucrose preference. Furthermore, estrogen-withdrawn females had more oxytocin-immunoreactive cells and oxytocin mRNA in the PVH, as well as an increase in oxytocin receptor density in the dorsal raphe nucleus (DRN). Finally, blocking oxytocin receptors in the DRN during estrogen withdrawal prevented the high-anxiety behavioral phenotype in estrogen-withdrawn females. ConclusionsEstrogen withdrawal alters oxytocin signaling in the PVH and DRN to increase anxiety-like behavior during the postpartum period. More broadly, these experiments suggest Syrian hamsters as a novel organism in which to model the effects of postpartum estrogen withdrawal on the brain and anxiety-like behavior.

neuroscience↗

bioRxiv2020

Binding affinities of oxytocin, vasopressin, and Manning Compound at oxytocin and V1a receptors in Syrian hamster brains

Oxytocin (OT) and arginine vasopressin (AVP), as well as synthetic ligands targeting their receptors (OTR, V1aR), are used in a wide variety of research contexts, but typically their pharmacological properties are determined in only a few species. Syrian hamsters (Mesocricetus auratus) have a long history of use as a behavioral and biomedical model for the study of oxytocin and vasopressin, and more recently, hamsters have been used to investigate behavioral consequences of OT-mediated activation of V1aRs. We sought to determine the binding affinities of OT, AVP, and the selective V1aR antagonist, Manning compound, in OTRs and V1aRs found in hamster brains. We performed saturation binding asays to determine the Kd values for the selective OTR and V1aR radioligands, [125I]OVTA and [125I]LVA in hamster brains. We then performed competition binding assays to determine Ki values for OT, AVP, and Manning compond at both the OTR and V1aR. We found that OT and AVP each had the highest affinity for their canonical receptors (OT-OTR Ki=4.28 nM; AVP-V1ar Ki=4.70 nM), and had the lowest affinity for their non-canonical ligands (OT-V1aR=495.2nM; AVP-OTR Ki=36.1 nM). Manning compound had the highest affinity for the V1aR (MC-V1aR Ki=6.87 nM; MC-OTR Ki=213.8 nM), but Manning compound was not as selective for the V1aR as has been reported in rat receptor. When comparing these data to previously published work, we found that the promiscuity of the V1aR in hamsters with respect to oxytocin and vasopressin binding is more similar to the promiscuity of the human V1aR than the rat V1aR receptor. Moreover, the selectivity of oxytocin at hamster receptors is more similar to the selectivity of oxytocin at human receptors than the selectivity of oxytocin at rat receptors. These data highlight the importance of determining the pharmacological properties of behaviorally relevant compounds in diverse models species.

neuroscience↗