Oxytocin improves long-lasting spatial memory during motherhood through MAP kinase cascade

Kazuhito Tomizawa; Norichika Iga; Yun-Fei Lu; Akiyoshi Moriwaki; Masayuki Matsushita; Sheng-Tian Li; Osamu Miyamoto; Toshifumi Itano; Hideki Matsui

doi:10.1038/nn1023

Oxytocin improves long-lasting spatial memory during motherhood through MAP kinase cascade

Nat Neurosci. 2003 Apr;6(4):384-90. doi: 10.1038/nn1023.

Authors

Kazuhito Tomizawa¹, Norichika Iga, Yun-Fei Lu, Akiyoshi Moriwaki, Masayuki Matsushita, Sheng-Tian Li, Osamu Miyamoto, Toshifumi Itano, Hideki Matsui

Affiliation

¹ Department of Physiology, Okayama University Graduate School of Medicine and Dentistry, Shikata-cho 2-5-1, Okayama 700-8558, Japan. [email protected]

PMID: 12598900
DOI: 10.1038/nn1023

Abstract

Oxytocin is an essential hormone for mammalian labor and lactation. Here, we show a new function of oxytocin in causing plastic changes in hippocampal synapses during motherhood. In oxytocin-perfused hippocampal slices, one-train tetanus stimulation induced long-lasting, long-term potentiation (L-LTP) and phosphorylation of cyclic AMP-responsive element binding protein (CREB), and MAP kinase inhibitors blocked these inductions. An increase in CREB phosphorylation and L-LTP induced by one-train tetanus were observed in the multiparous mouse hippocampus without oxytocin application. Furthermore, intracerebroventricular injection of oxytocin in virgin mice improved long-term spatial learning in vivo, whereas an injection of oxytocin antagonist in multiparous mice significantly inhibited the improved spatial memory, L-LTP and CREB phosphorylation. These findings indicate that oxytocin is critically involved in improving hippocampus-dependent learning and memory during motherhood in mice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cyclic AMP Response Element-Binding Protein / drug effects
Cyclic AMP Response Element-Binding Protein / metabolism
Electric Stimulation
Enzyme Inhibitors / pharmacology
Hippocampus / drug effects
Hippocampus / enzymology*
Injections, Intraventricular
Lactation / drug effects
Lactation / physiology*
Learning / drug effects
Learning / physiology
Long-Term Potentiation / drug effects
Long-Term Potentiation / physiology*
MAP Kinase Signaling System / drug effects
MAP Kinase Signaling System / physiology
Maternal Behavior / drug effects
Maternal Behavior / physiology
Memory / drug effects
Memory / physiology*
Mice
Neural Pathways / drug effects
Neural Pathways / enzymology
Neurons / drug effects
Neurons / enzymology
Organ Culture Techniques
Oxytocin / antagonists & inhibitors
Oxytocin / metabolism*
Phosphorylation / drug effects
Space Perception / drug effects
Space Perception / physiology*
Up-Regulation / drug effects
Up-Regulation / physiology

Substances

Cyclic AMP Response Element-Binding Protein
Enzyme Inhibitors
Oxytocin