Abstract
Neuropeptide S (NPS) has been shown to promote arousal and anxiolytic-like effects, as well as facilitation of fear extinction. In rodents, NPS receptors (NPSR) are prominently expressed in brain structures involved in learning and memory. Here, we investigate whether exogenous or endogenous NPS signaling can modulate acquisition, consolidation, or recall of emotional, spatial, and contextual memory traces, using two common behavioral paradigms, inhibitory avoidance (IA) and novel object recognition. In the IA paradigm, immediate and delayed post-training central NPS administration dose dependently enhanced memory retention in mice, indicating that NPS may act during the consolidation phase to enhance long-term memory. In contrast, pre-training or pre-test NPS injections were ineffective, suggesting that NPS had no effect on IA memory acquisition or recall. Peripheral administration of a synthetic NPSR antagonist attenuated NPS-induced IA memory enhancement, showing pharmacological specificity. NPS also enhanced hippocampal-dependent non-aversive memory in the novel object recognition task. In contrast, NPSR knockout mice displayed deficits in IA memory, novel object recognition, and novel place or context recognition, suggesting that activity of the endogenous NPS system is required for memory formation. Blockade of adrenergic signaling by propranolol attenuated NPS-induced memory enhancement in the IA task, indicating involvement of central noradrenergic systems. These results provide evidence for a facilitatory role of NPS in long-term memory, independent of memory content, possibly by acting as a salience signal or as an arousal-promoting factor.
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Acknowledgements
We gratefully acknowledge scientific support by Drs Benno Roozendaal and Marcelo Wood (University of California, Irvine, CA), Natalie Rodrigue (Creascience, Montreal, Canada) for help with statistical analysis, and Dr Beverly H Koller (University of North Carolina at Chapel Hill) for making NPSR knockout mice available. This work was supported in part by a National Institute of Mental Health Grant (MH-71313; RKR), a postdoctoral fellowship from the Mitsubishi Pharma Research Foundation (NO), a training grant fellowship from the National Institute on Drug Abuse (DMD), a post-doctoral fellowship from the Canadian Institutes of Health Research (SDC), and a grant from the Deutsche Forschungsgemeinschaft (SFB-TRR58, TP A03; HCP), the Max-Planck Society, and Humboldt Foundation (Research Award 2007; HCP).
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Okamura, N., Garau, C., Duangdao, D. et al. Neuropeptide S Enhances Memory During the Consolidation Phase and Interacts with Noradrenergic Systems in the Brain. Neuropsychopharmacol 36, 744–752 (2011). https://doi.org/10.1038/npp.2010.207
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DOI: https://doi.org/10.1038/npp.2010.207
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