Homer1 proteins and AMPA receptors modulate cocaine-induced behavioural plasticity

M. Behnam Ghasemzadeh, Lindsay K. Permenter, Russell Lake, Paul F Worley, Peter W. Kalivas

Research output: Contribution to journalArticle

Abstract

Homer proteins form functional assemblies in the excitatory postsynaptic density, and withdrawal from repeated cocaine administration reduces the expression of Homer1b/c in the nucleus accumbens. To determine if the reduction in Homer1b/c may be contributing to cocaine-induced behavioural sensitization, antisense oligonucleotides were infused over two weeks into the nucleus accumbens of rats to reduce Homer1 gene expression by approximately 35%. Infusion of antisense sequences (AS1 and AS2) caused a sensitization-like augmentation in the motor response to acute cocaine administration in naive rats. One of the sequences (AS1) also prevented the development of sensitization to repeated cocaine treatment, while AS2 was without effect. A panel of immunoblots for other proteins in the excitatory postsynaptic density revealed that AS1, but not AS2 reduced the level of the α -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit GluR1 protein. This posed the possibility that altered AMPA signalling may mediate the inhibitory effect of AS1 on the development of sensitization. To examine this possibility, rats were pretreated in the accumbens with drugs to block AMPA/kainate, N-methyl-D-aspartate, group 1 metabotropic glutamate or dopamine receptors prior to each daily injection of cocaine. Only AMPA/kainate receptor blockade prevented the development of behavioural sensitization to cocaine. These data indicate that the expression of behavioural sensitization arises in part from a reduction in Homer1 gene products in the accumbens, while the development of sensitization requires stimulation of AMPA/kainate receptors.

Original languageEnglish (US)
Pages (from-to)1645-1651
Number of pages7
JournalEuropean Journal of Neuroscience
Volume18
Issue number6
DOIs
StatePublished - Sep 2003

Fingerprint

Cocaine
Post-Synaptic Density
Kainic Acid Receptors
Proteins
Nucleus Accumbens
Metabotropic Glutamate Receptors
Antisense Oligonucleotides
Kainic Acid
Dopamine Receptors
Protein Subunits
N-Methylaspartate
propionic acid
bucide
cocaine receptor
Gene Expression
Injections
Pharmaceutical Preparations
Genes

Keywords

  • Antisense
  • Glutamate
  • Nucleus accumbens
  • Rat
  • Sensitization

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Homer1 proteins and AMPA receptors modulate cocaine-induced behavioural plasticity. / Ghasemzadeh, M. Behnam; Permenter, Lindsay K.; Lake, Russell; Worley, Paul F; Kalivas, Peter W.

In: European Journal of Neuroscience, Vol. 18, No. 6, 09.2003, p. 1645-1651.

Research output: Contribution to journalArticle

Ghasemzadeh, M. Behnam ; Permenter, Lindsay K. ; Lake, Russell ; Worley, Paul F ; Kalivas, Peter W. / Homer1 proteins and AMPA receptors modulate cocaine-induced behavioural plasticity. In: European Journal of Neuroscience. 2003 ; Vol. 18, No. 6. pp. 1645-1651.
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