Chronic dopaminergic signaling in the basal ganglia: a damage perspective on kinases and fos-related antigens.
O'Callaghan JP; Miller DB; Pennypacker KR
Addiction Biol 2000 Jul-Sep; 5(3):369-376
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.
Antigens; Proteins; Drug abuse; Drugs; Nerve damage; Neurotoxicity; Neurotoxic effects; Neurotoxins; Neurotoxicology
James P. O'Callaghan PhD, Centers for Disease Control and Prevention, NIOSH/HELD/TMBB (MS-3014), 1095 Willowdale Road, Morgantown, WV 26505-2888, USA