Cocaine alters catalase activity in prefrontal cortex and striatum of mice.
Catalase is one of the enzymes that convert hydrogen peroxide (H2O2) to H2O presenting a protective role against free radicals. In this study, catalase activity was determined in homogenates of striatum (ST) and prefrontal cortex (PFC) in order to examine the participation of oxidative stress (OS) on cocaine actions in mice brain. Male Swiss mice were injected (i.p.) with cocaine at low (10 and 30 mg/kg) and high doses (90 mg/kg), and observed for 1 h. After cocaine overdose (90 mg/kg) some animals presented only status epilepticus (SE) while others died after seizures. These animals were dissected and divided in two groups, SE and death. Catalase activity was also determined after pretreatment with the anticonvulsant drug, diazepam, alone or injected before cocaine 90 mg/kg, and after seizures induced by a high dose of bupropion, a known inhibitor of NE and DA reuptake used for comparison. Results showed a decrease in catalase activity of the PFC and ST after SE and death induced by cocaine and bupropion overdoses. Cocaine at low doses decreased the enzyme activity only in ST. Diazepam treatment alone and before cocaine overdose did not interfere with catalase activity. This reduction in catalase activity may reflect an increase in H2O2 content in PFC and ST. Previous data reports that H2O2 inhibits dopamine transporter activity, suggesting that the decrease in catalase activity may potentiate the toxic mechanism of drugs that inhibit monoamines reuptake. As far as we know, this is the first report showing an involvement of OS in the cocaine's central mechanism of action.
Macêdo
Danielle Silveira
DS
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, 60431-970 Fortaleza, Ceará, Brazil. daniellesm2000@yahoo.com
de Vasconcelos
Silvânia Maria Mendes
SM
dos Santos
Rachel Silva
RS
Aguiar
Lissiana Magna Vasconcelos
LM
Lima
Vera Targino Moreira
VT
Viana
Glauce Socorro Barros
GS
de Sousa
Francisca Cléa Florenço
FC
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D016642:Bupropion / Q000494:pharmacology; D002374:Catalase / Q000187:drug effects* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D003042:Cocaine / Q000009:adverse effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D003975:Diazepam / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D009026:Mortality; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D012640:Seizures / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D013226:Status Epilepticus / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology
D018759:Adrenergic Uptake Inhibitors; D000927:Anticonvulsants; D002395:Catecholamines; D018765:Dopamine Uptake Inhibitors; D016166:Free Radical Scavengers; D016642:Bupropion; D006861:Hydrogen Peroxide; D002374:Catalase; D003042:Cocaine; D003975:Diazepam