title: Opiate withdrawal induces dynamic expressions of AMPA receptors and its regulatory molecule CaMKIIalpha in hippocampal synapses.
abstract: Adaptive changes in brain areas following drug withdrawal are believed to contribute to drug seeking and relapse. Cocaine withdrawal alters the expression of GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in nucleus accumbens or amygdala, but the influence of drug withdrawal on hippocampus is little known. Here, we have examined the expression of GluR1 and GluR2/3 in hippocampal membrane and synaptic fractions following repeated morphine exposure and subsequent withdrawal. Repeated morphine exposure for 12 d increased GluR1 and GluR2/3 in synaptosome but not in membrane fraction. Interestingly, CaMKIIalpha, known to be able to regulate the function of AMPA receptors, was decreased in synaptosome but not in membrane fraction; pCaMKIIalpha, the phosphorylated form of CaMKIIalpha, was increased in both fractions. However, during opiate withdrawal, GluR1 was generally reduced while GluR2/3 was prominently increased in both fractions; pCaMKIIalpha was strongly decreased immediately after withdrawal, but detectably increased in late phase of morphine withdrawal in both fractions. Importantly, the opiate withdrawal-induced increase in GluR2/3 was dependent on the activation of glucocorticoid receptors and NMDA receptors, as it was prevented by the glucocorticoid receptor antagonist RU38486, or intrahippocampal injection of the NMDA receptor antagonist AP-5 or the antagonist to NR2B-containing NMDA receptors, Ro25-6981. These findings indicate that opiate withdrawal induces dynamic expression of GluR1 and GluR2/3 subunits of AMPA receptors in hippocampal synapses, possibly revealing an adaptive process of the hippocampal functions following opiate withdrawal.
authors.affiliation: Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310006, PR China.
authors.forename: Weixia
authors.initials: W
authors.lastname: Zhong
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Dong
authors.forename: Meng
authors.initials: M
authors.lastname: Tian
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Tianle
authors.initials: T
authors.lastname: Xu
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Jianhong
authors.initials: J
authors.lastname: Luo
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis*; D002462:Cell Membrane / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009020:Morphine / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013315:Stress, Psychological / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D008565:Membrane Proteins; D009020:Morphine; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor; C104722:glutamate receptor ionotropic, AMPA 2