Cocaine treatment increases expression of a 40 kDa catecholamine-regulated protein in discrete brain regions.
Previous reports from our laboratory have described brain-specific catecholamine-regulated proteins, which bind dopamine and related catecholamines. Evidence from the molecular cloning of a 40 kDa catecholamine-regulated protein (CRP40) revealed that CRP40 is dopamine-inducible and has properties similar to those of the 70 kDa heat shock protein (HSP70) family. The present study investigates the effects of acute and chronic cocaine treatment on CRP40 expression in the striatum, nucleus accumbens, prefrontal cortex, and medulla. Acute treatment with cocaine increased CRP40 expression in the nucleus accumbens and striatum, whereas chronic treatment with cocaine increased CRP40 expression in the nucleus accumbens only. Neither of these treatments affected CRP40 levels in the prefrontal cortex or medulla. In addition, pretreatment with the spin-trapping agent alpha-phenyl-tert-butylnitrone did not attenuate cocaine-induced expression of CRP40, suggesting that the observed increases in CRP40 levels were not caused by free radicals. On the other hand, pretreatment with anisomycin, a protein synthesis inhibitor, blocked the cocaine-induced expression of CRP40. Thus, protein synthesis may be involved in the observed CRP40 level increases. Furthermore, neither acute nor chronic cocaine treatment affected levels of inducible or constitutively expressed HSP70, which indicates a specificity of cocaine's effects on CRP40. Since cocaine has been shown to increase extracellular dopamine levels, these findings suggest that increased expression of CRP40 is associated with high extracellular levels of dopamine (or its metabolites). Elevated levels of CRP40 could play a protective role for dopamine neurons in response to increased oxidative stress that has been shown to be induced by cocaine and that can lead to apoptosis and neurodegeneration.
Sharan
Niki
N
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada.
Chong
Victor Z
VZ
Nair
Venugopalan D
VD
Mishra
Ram K
RK
Hayes
Robert J
RJ
Gardner
Eliot L
EL
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003497:Cyclic N-Oxides; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005110:Extracellular Space / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D003497:Cyclic N-Oxides; D018765:Dopamine Uptake Inhibitors; D016166:Free Radical Scavengers; D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D011500:Protein Synthesis Inhibitors; C422207:catecholamine-regulated protein, 40 kDa; C029217:phenyl-N-tert-butylnitrone; D000841:Anisomycin; D003042:Cocaine; D004298:Dopamine