Oxytocin Protects Hippocampal Memory and Plasticity from Uncontrollable Stress

Abstract

The hippocampus is vulnerable to uncontrollable stress and is enriched with oxytocin receptors, but their interactive influences on hippocampal functioning are unknown. This study aimed to determine the effects of intranasal oxytocin administration on stress-induced alterations in synaptic plasticity and spatial memory in male rats. While vehicle-administered stressed rats showed impairment in long-term potentiation, enhancement in long-term depression, and weakened spatial memory, these changes were not observed in oxytocin-administered stressed rats. To reveal the potential signaling mechanism mediating these effects, levels of phosphorylated extracellular signal-regulated kinases (pERK) in the hippocampus was examined. Western blotting showed that oxytocin treatment blocked stress-induced alterations of pERK. Additionally, the oxytocin receptor antagonist L-368,899 inhibited the oxytocin’s protective effects on hippocampal memory to stress. Thus, intranasal administration of oxytocin reduced stress effects on hippocampal synaptic plasticity and memory in rats via acting on oxytocin receptors and regulating ERK activity. This study suggests that exogenous oxytocin may be a therapeutically effective means to counter the detrimental neurocognitive effects of stress.

Preliminary Data on Some Behavioral Changes Induced by Short-Term Intraperitoneal Oxytocin Administration in Aged Rats

“…Kunchiulia et al (2010) showed that OT administration before stress exposing does not cause memory impairment prevention. Also, Sun-Young Lee et al (2015) reports decreased cumulative search error, higher swim speed, and increased time in target annulus in OT treated rats, as compared with control group in the Morris water maze memory test. These findings together with our results suggest that OT may influence hippocampal activity and memory acquisition in rats.…”

Oxytocin and vasopressin in the rodent hippocampus

“…Oxt does not alter LTP induction but does enhance long‐lasting LTP (L‐LTP) in the CA1 region in mice of either sex or male rats and is seen in both the dorsal and ventral CA1 region . Oxt is also capable of rescuing LTP induction in stressed rats . Mechanistically, the Oxt‐induced enhancement of L‐LTP requires translation but not transcription and is sensitive to inhibitors of phospholipase C, protein kinase Mζ, and the mammalian target of rapamycin protein kinase …”

“…139 Oxt is also capable of rescuing LTP induction in stressed rats. 138,140 Mechanistically, the Oxt-induced enhancement of L-LTP requires translation but not transcription and is sensitive to inhibitors of phospholipase C, protein kinase Mζ, and the mammalian target of rapamycin protein kinase. 139 Application of Avp induces a long-lasting enhancement of excitatory drive onto the ventral CA1 region in male rats.…”

Binding to and Inhibition of Insulin-Regulated Aminopeptidase by Macrocyclic Disulfides Enhances Spine Density

“…Notably, the IRAP inhibitor Ang IV has been shown to increase levels of oxytocin in the brain in vivo (Beyer et al, 2010). The hippocampus is enriched with oxytocin receptors (Lee et al, 2015) and oxytocin has been shown to stimulate adult neurogenesis in the hippocampus (Leuner et al, 2012) and enhance LTP in the CA1 region (Lin et al, 2012). Therefore, the potential procognitive effects of IRAP inhibitors may be mediated by increases in the levels and prolongation of activity of substrates including oxytocin.…”