Ketamine induces hippocapal mitochondrial dysfunction

CEZRNICZYNIEC ANALIA; KARADAYIAN ANALÍA GRACIELA; BUSTAMANTE JUANITA; LORES-ARNAIZ SILVIA

Buenos Aires

Congreso; VIII International Congress Society for Free Radical Biology and Medicine South American Group; 2013

Ketamine, an N-methyl-D-aspartate receptor antagonist (NMDA), is able to induce neuronal apoptosis in developing rodents. The aim of this work was to evaluate the cortical and hippocampal mitochondrial changes after ketamine exposure. Male Sprague-Dawley pups received ketamine (40 mg/Kg i.p.) for 3 consecutive days. Oxygen consumption, hydrogen peroxide production, mitochondrial membrane potential, respiratory complexes activity and nitric oxide production were measured. Malate-glutamate state 4 oxygen consumption was decreased by 35 % and succinate-dependent state 4 respiratory rate was increased 1.3 fold in hippocampal mitochondria from treated animals. No significant changes were observed in state 3 oxygen consumption using both respiratory substrates. Evaluation of hydrogen peroxide production by hippocampal mitochondria from treated animals showed a significant increase of 26 %. Ketamine induced hippocampal mitochondrial depolarization (10%) and decreased Complex I activity (20 %). Also, nitric oxide production decreased by 22% after treatment. However, no changes were observed in any of these parameters in cortical mitochondria from ketamine-treated animals. The above results show that systemic administration of ketamine to male pups during 3 days induces mitochondrial dysfunction. The impairment of mitochondrial function could be related to the initial steps of the apoptosis process.