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


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.

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Figure 1: The expression of oxytocin receptor in the hippocampus of female mice.
Figure 2: The effect of oxytocin on basal neurotransmission, LTP and L-LTP.
Figure 3: Inhibition of oxytocin-induced L-LTP and CREB phosphorylation by a MAP kinase inhibitor.
Figure 4: Comparison of L-LTP and CREB phosphorylation in the hippocampus between nulliparous and multiparous mice.
Figure 5: The effect of oxytocin antagonist on the expression of CREB (a), L-LTP (b) and spatial learning (c) in the hippocampus of multiparous mice.


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We thank N. Janjua for proofreading this manuscript. This study was carried out as a part of the Ground-based Research Announcement for Space Utilization, promoted by the Japan Space Forum and by the Industrial Technology Research Grant Program in 2002 from New Energy and Industrial Technology Development Organization (NEDO), Japan.

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Correspondence to Kazuhito Tomizawa.

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Tomizawa, K., Iga, N., Lu, YF. et al. Oxytocin improves long-lasting spatial memory during motherhood through MAP kinase cascade. Nat Neurosci 6, 384–390 (2003).

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