Incubation of Methamphetamine Craving Is Associated with Selective Increases in Expression of Bdnf and Trkb, Glutamate Receptors, and Epigenetic Enzymes in Cue-Activated Fos-Expressing Dorsal Striatal Neurons

作者: X. Li , F. J. Rubio , T. Zeric , J. M. Bossert , S. Kambhampati

DOI: 10.1523/JNEUROSCI.1022-15.2015

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摘要: Cue-induced methamphetamine seeking progressively increases after withdrawal (incubation of craving), but the underlying mechanisms are largely unknown. We determined whether this incubation is associated with alterations in candidate genes dorsal striatum (DS), a brain area implicated cue- and context-induced drug relapse. first measured mRNA expression 24 whole DS extracts short (2 d) or prolonged (1 month) rats following extended-access saline (control condition) self-administration (9 h/d, 10 d). found minimal changes. Next, using fluorescence-activated cell sorting, we compared gene Fos-positive striatal neurons, which were activated during "incubated" cue-induced drug-seeking tests withdrawal, nonactivated Fos-negative neurons. significant immediate early (Arc, Egr1), Bdnf its receptor (Trkb), glutamate subunits (Gria1, Gria3, Grm1), epigenetic enzymes (Hdac3, Hdac4, Hdac5, GLP, Dnmt3a, Kdm1a) neurons only. Using RNAscope to determine subregion cell-type specificity colabeling Fos Drd1 Drd2 three subregions. was neither nor specific (52.5 39.2% colabeled Drd2, respectively). Finally, that injections SCH23390 (C17H18ClNO), D1-family antagonist known block induction, decreased incubated withdrawal. Results demonstrate critical role craving selective gene-expression cue-activated D1- D2-expressing

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