title: Acute treatment with doxorubicin induced neurochemical impairment of the function of dopamine system in rat brain structures.
abstract: BACKGROUND
  The clinical studies have shown that chemotherapy may impair cognitive functions especially in the patients treated for breast cancer. It should be mention that only few studies have made use of animals to investigate the effects of chemotherapy on the brain function. Doxorubicin (Adriamycin) is an anthracycline antibiotic commonly used for chemotherapy of breast cancer.
  
  
  METHODS
  This study examined the effect of doxorubicin (1.5 and 3.0mg/kg ip) after acute administration on the levels of dopamine, noradrenaline, serotonin and their metabolites in the rat brain structures connected with cognition and psychiatric disorders.
  
  
  RESULTS
  The data indicate that doxorubicin produced a significant and specific for the dopamine system inhibition of its activity in the investigated structures connected with the fall of dopamine concentration (decrease from 25 to 30% in the frontal cortex; from 30 to 60% in the hippocampus and about 20% of the control in the striatum, p<0.05) and its extraneuronal metabolite, 3-MT (from 35% in the frontal cortex to 60% in the hippocampus of the control level, p<0.01). However, doxorubicin did not affect others monoaminergic transmitters in the brain: noradrenaline and serotonin.
  
  
  CONCLUSIONS
  Summing up, these data indicate that a single injection of doxorubicin produced a clear and significant inhibition of dopamine system activity in all investigated structures with the strongest effect in the hippocampus what may lead to the disturbances of the cognitive functions at the patients treated for cancer. Moreover, such treatment did not significantly affect others monoaminergic transmitters such as noradrenaline and serotonin.
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Science, Kraków, Poland. Electronic address: antkiew@if-pan.krakow.pl.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Antkiewicz-Michaluk
authors.affiliation: Department of Oncology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Krzemieniecki
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Science, Kraków, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Romanska
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Science, Kraków, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Michaluk
authors.affiliation: Department of Neurology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Krygowska-Wajs
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism
chemical_list: D012701:Serotonin; D004317:Doxorubicin; D004298:Dopamine; D009638:Norepinephrine
keywords: Doxorubicin; HPLC; Monoamines metabolism; Rat brain structures