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

Authors
O'Callaghan-JP; Miller-DB; Pennypacker-KR
Source
Addiction Biol 2000 Jul-Sep; 5(3):369-376
NIOSHTIC No.
20020767
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.
Keywords
Antigens; Proteins; Drug-abuse; Drugs; Nerve-damage; Neurotoxicity; Neurotoxic-effects; Neurotoxins; Neurotoxicology
Contact
James P. O'Callaghan PhD, Centers for Disease Control and Prevention, NIOSH/HELD/TMBB (MS-3014), 1095 Willowdale Road, Morgantown, WV 26505-2888, USA
CODEN
ADBIFN
Publication Date
20000701
Document Type
Journal Article
Email Address
jdo5@cdc.gov
Fiscal Year
2000
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
1355-6215
NIOSH Division
HELD
Source Name
Addiction Biology
State
WV; FL
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