Differential modulation of drug-induced structural and functional plasticity of dendritic spines

Eric C. Miller, Lei Zhang, Benjamin W. Dummer, Desmond R. Cariveau, Horace H Loh, Ping-Yee Law, Dezhi Liao

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)333-343
Number of pages11
JournalMolecular Pharmacology
Volume82
Issue number2
DOIs
StatePublished - Aug 1 2012

Fingerprint

Dendritic Spines
KN 62
Neuronal Plasticity
Tacrolimus
Pharmaceutical Preparations
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
AMPA Receptors
Calcineurin
Electrophysiology
Street Drugs
Opioid Receptors
Synaptic Transmission
Synapses
Immunohistochemistry
Learning
Neurons
Acids
Inhibition (Psychology)

Cite this

Differential modulation of drug-induced structural and functional plasticity of dendritic spines. / Miller, Eric C.; Zhang, Lei; Dummer, Benjamin W.; Cariveau, Desmond R.; Loh, Horace H; Law, Ping-Yee; Liao, Dezhi.

In: Molecular Pharmacology, Vol. 82, No. 2, 01.08.2012, p. 333-343.

Research output: Contribution to journalArticle

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