The membrane cytoskeletal protein adducin is phosphorylated by protein kinase C in D1 neurons of the nucleus accumbens and dorsal striatum following cocaine administration.
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.
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut, USA.
Jérémie
J
Lavaur
Yann S
YS
Mineur
Marina R
MR
Picciotto
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D053119:Benzophenanthridines / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D020891:Raclopride / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D013997:Time Factors; D000099291:Adducins
D001552:Benzazepines; D053119:Benzophenanthridines; D002148:Calmodulin-Binding Proteins; D003042:Cocaine; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D049452:Green Fluorescent Proteins; D011493:Protein Kinase C; D020891:Raclopride; D017447:Receptors, Dopamine D1; D000099291:Adducins; C534628:SCH 23390; C485184:enhanced green fluorescent protein; C016299:chelerythrine