title: Differential modulation of drug-induced structural and functional plasticity of dendritic spines.
abstract: Drug-induced plasticity of excitatory synapses has been proposed to be the cellular mechanism underlying the aberrant learning associated with addiction. Exposure to various drugs of abuse causes both morphological plasticity of dendritic spines and functional plasticity of excitatory synaptic transmission. Chronic activation of μ-opioid receptors (MOR) in cultured hippocampal neurons causes two forms of synaptic plasticity: loss of dendritic spines and loss of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. With use of live imaging, patch-clamp electrophysiology, and immunocytochemistry, the present study reveals that these two forms of synaptic plasticity are mediated by separate, but interactive, intracellular signaling cascades. The inhibition of Ca(2+)/calmodulin-dependent protein kinase II with 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-62) blocks MOR-mediated structural plasticity of dendritic spines, but not MOR-mediated cellular redistribution of GluR1 and GluR2 AMPA receptor subunits. In contrast, the inhibition of calcineurin with tacrolimus (FK506) blocks both cellular processes. These findings support the idea that drug-induced structural and functional plasticity of dendritic spines is mediated by divergent, but interactive, signaling pathways.
authors.affiliation: Graduate Program in Neuroscience, Department of Neuroscience, University of Minnesota Medical School, 321 Church St. SE, Minneapolis, MN 55455, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Miller
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Dummer
authors.forename: Desmond R
authors.initials: DR
authors.lastname: Cariveau
authors.forename: Horace
authors.initials: H
authors.lastname: Loh
authors.forename: Ping-Yee
authors.initials: PY
authors.lastname: Law
authors.forename: Dezhi
authors.initials: D
authors.lastname: Liao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D009020:Morphine