blocking mineralocorticoid receptors prior to retrieval reduces contextual fear memory in mice检索之前阻止盐皮质激素受体减少上下文小鼠的恐惧记忆.pdfVIP

Blocking Mineralocorticoid Receptors prior to Retrieval Reduces Contextual Fear Memory in Mice 1 2 ¨ 1,3 1 Ming Zhou , Merel Kindt , Marian Joels , Harm J. Krugers * 1 Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands, 2 Department of Clinical Psychology, University of Amsterdam, Amsterdam, The Netherlands, 3 Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands Abstract Background: Corticosteroid hormones regulate appraisal and consolidation of information via mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) respectively. How activation of these receptors modulates retrieval of fearful information and the subsequent expression of fear is largely unknown. We tested here whether blockade of MRs or GRs during retrieval also affects subsequent expression of fear memory. Methodology/Principal Findings: Mice were trained in contextual or tone cue fear conditioning paradigms, by pairing mild foot shocks with a particular context or tone respectively. Twenty-four hours after training, context-conditioned animals were re-exposed to the context for 3 or 30 minutes (day 2); tone-conditioned animals were placed in a different context and re-exposed to one or six tones. Twenty-four hours (day 3) and one month later, freezing behavior to the aversive context/ tone was scored again. MR or GR blockade was achieved by giving spironolactone or RU486 subcutaneously one hour before retrieval on day 2. Spironolactone administered prior to brief context re-exposure reduced freezing behavior during retrieval and 24 hours later, but not one month later. Administration of s