Chronic dopaminergic signaling in the basal ganglia: A damage perspective on kinases and fos-related antigens

James P. O'Callaghan, Diane B. Miller, Keith R. Pennypacker

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Specific protein phosphorylation pathways have been shown to play a role in cellular adaptation responses underlying addiction to psychostimulants such as methamphetamine and cocaine. Transcriptional regulation through fos-related antigens constitutes one element through which these dopaminergic agonists exert their persistent actions. In addition to their addictive properties, amphetamines are Known to damage dopaminergic nerve terminals. Although not widely appreciated, protein phosphorylation cascades and fos-related antigens also may play a role in the neurotoxic actions of substituted amphetamines such as methamphetamine. Here we document the involvement of the dopaminoceptive phosphoprotein, DARPP-32, the fos-related antigen, FRA-2, and the growth associated protein kinase, MAP kinase, in the neurotoxic action of known dopaminergic neurotoxicants, including methamphetamine. The addictive and neurotoxic properties of psychostimulants may share some molecular signaling mechanisms.

Original languageEnglish
Pages (from-to)369-376
Number of pages8
JournalAddiction Biology
Volume5
Issue number3
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

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