The membrane cytoskeletal protein adducin is phosphorylated by protein kinase C in D1 neurons of the nucleus accumbens and dorsal striatum following cocaine administration

J Neurochem. 2009 Dec;111(5):1129-37. doi: 10.1111/j.1471-4159.2009.06405.x. Epub 2009 Sep 24.

Abstract

Repeated cocaine administration results in persistent changes in synaptic function in the mesolimbic dopamine system that are thought to be critical for the transition to addiction. Cytoskeletal rearrangement and actin dynamics are essential for this drug-dependent plasticity. Cocaine administration increases levels of F-actin in the nucleus accumbens and is associated with changes in the phosphorylation state of actin-binding proteins. The adducins constitute a family of proteins that interact with actin and spectrin to maintain cellular architecture. The interaction of adducin with these cytoskeletal proteins is regulated by phosphorylation, and it is therefore expected that phosphorylation of adducin may be involved in morphological changes underlying synaptic responses to drugs of abuse including cocaine. In the current study, we characterized the regulation of adducin phosphorylation in the nucleus accumbens and dorsal striatum in response to various regimen of cocaine. Our results demonstrate that adducin is phosphorylated by protein kinase C in medium spiny neurons that express the dopamine D1 receptor. These data indicate that adducin phosphorylation is a signaling event regulated by cocaine administration and further suggest that adducin may be involved in remodeling of the neuronal cytoskeleton in response to cocaine administration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzazepines / pharmacology
  • Benzophenanthridines / pharmacology
  • Calmodulin-Binding Proteins / deficiency
  • Calmodulin-Binding Proteins / metabolism*
  • Cocaine / pharmacology*
  • Corpus Striatum / cytology*
  • Corpus Striatum / drug effects
  • Dopamine Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / antagonists & inhibitors
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Green Fluorescent Proteins / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / drug effects*
  • Nucleus Accumbens / cytology*
  • Nucleus Accumbens / drug effects
  • Phosphorylation / drug effects
  • Protein Kinase C / metabolism*
  • Raclopride / pharmacology
  • Receptors, Dopamine D1 / physiology*
  • Time Factors

Substances

  • Benzazepines
  • Benzophenanthridines
  • Calmodulin-Binding Proteins
  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Enzyme Inhibitors
  • Receptors, Dopamine D1
  • SCH 23390
  • adducin
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Raclopride
  • chelerythrine
  • Protein Kinase C
  • Cocaine