Cognitive inflexibility induced by addictive drug is being associated to compulsive drug-seeking. Different cortex-striatum pathways specifically control different functional modules in cognitive flexibility, including extra-dimensional and intra-dimensional strategy transition. Our previous findings showed that chronic escalating dose of morphine could elicit addictive-like behaviors and also selectively impaired set-shifting in extra-dimensional strategy. Furthermore, we also found significantly parallel up-regulations of phosphoSer831-GluR1 and dendrite density in nucleus accumbens (NAc) core, as well as enhancement of phosphoSer845-GluR1 in dorsalmedial striatum. We are supposing that morphological and functional re-organization in striatum, especially NAc core, has a vital role in cognitive impairment produced by additive use of morphine. In this project, we will utilize many kinds of technologies, including molecular cloning, virus infect and immunofluorescence cellular chemistry, etc, determine relationship between phosphorylation of Glu1R and GluR1 trafficking in striatum in cognitive inflexibility that chronic morphine exposure leads to. We also further investigate the types of medium spine neurons (MSNs) (D1R positive expression or D2R positive expression) that GluR1 and dendrit plasticities occur to.
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