The metaplastic effects of NMDA receptors blockade on reactivation of instrumental memories in rats

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HIGHLIGHTSMK-801 given 24h before instrumental memory retrieval affected reconsolidation.Changes of Zif268 and rpS6P in key brain areas indicated reconsolidation inhibition.MK-801 given 24h before also increased glutamate receptors in a metaplastic fashion.‘Metaplastic’ MK-801 might facilitated extinction rather than inhibited reconsolidation.Metaplasticity, defined as the plasticity of synaptic plasticity, could affect learning and memory at different neural levels. It was hypothesized that metaplasticity changes on glutamate receptors may affect memory destabilization, promoting or preventing reconsolidation. We investigated the metaplastic effect of NMDA channel blocker MK-801 on sucrose instrumental memory reconsolidation in a behavioural rat model associated to the assessment of molecular markers of metaplasticity, memory retrieval, destabilization and reconsolidation.Following instrumental conditioning and forced abstinence, rats were intraperitoneally treated with MK-801 or vehicle 24h before the exposure to memory retrieval or not-retrieval. Separate groups were tested for in-vivo extinction of responding (24h and 7d after reactivation) or ex-vivo assessment of transcription factor Zif268 and ribosomal protein rpS6 phosphorylation in nucleus accumbens (NAc) and amygdala (Amy).MK-801 significantly inhibited instrumental responding at extinction test, suggesting reconsolidation blockade of instrumental memory. The decrease of Zif268 and phosphorylated-rpS6 levels in NAc and Amy in MK-801/Retrieval vs. Vehicle/Retrieval group supported the behavioural findings. An increase of GluN2B, GluA1 and mGluR5 in NAc, and GluN2B in Amy, 24h after MK-801 indicated the trigger of associated metaplastic changes.Our findings show that metaplastic changes induced by NMDA receptors blockade affected sucrose instrumental memory retrieval as shown by both behavioural and molecular changes. We hypothesize that these findings however suggested a switch to extinction rather than a reconsolidation.

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