Ketamine prevents lidocaine-caused neurotoxicity in the CA3 hippocampal and basolateral amygdala regions of the brain in adult rats.
Our objective was to prove whether blocking the action of glutamate on N-methyl-D: -aspartate (NMDA) receptors could prevent the neuronal damage caused by the acute administration of lidocaine. Twenty male 2-month-old Wistar rats were randomly assigned to the following groups (n = 5 in each group): groups I and II received 0.9% saline i.p., and groups III and IV received 100 mg x kg(-1) of ketamine i.p. Thirty minutes later, groups I and III were again dosed with 0.9% saline i.p., and groups II and IV received 60 mg x kg(-1) of lidocaine i.p. During treatment, the rectal temperature of the animals was monitored and maintained at 37.5 +/- 0.5 degrees C. Ten days after administration of the agents, all rats were transcardially perfused, under pentobarbital anesthesia, with 10% formaldehyde. Their brains were removed and were embedded in paraffin. Coronal cuts of 7 microm were obtained from -2.3 to -3.8 mm from the bregma. Each brain section was stained with cresyl violet-eosin. The number of normal and abnormal pyramidal neurons in the CA3 hippocampal region and the number of large and medium neurons in the basolateral amygdala within an area of 10 000 microm2 were evaluated. We found that lidocaine significantly reduced the number of normal neurons in both the CA3 hippocampal region (F (3,16) = 225.8; P < 0.001) and the basolateral amygdala (F (3,16) = 253.3; P < 0.001). The ketamine pretreatment attenuated the lidocaine-induced damage in the CA3 hippocampal region and the basolateral amygdala. These results demonstrate the participation of NMDA-receptor activation by lidocaine in the CA3 hippocampal and basolateral amygdala regions as a neurotoxic mechanism.
Lopez-Galindo
Gabriel Eduardo
GE
Departamento de Fisiología "Mauricio Russek Berman" de la Escuela Nacional de Ciencias Biológicas, I.P.N., Carpio y Plan de Ayala, México City, 11340, Mexico.
Cano-Europa
Edgar
E
Ortiz-Butron
Rocio
R
D000679:Amygdala / Q000473:pathology*; D000779:Anesthetics, Local / Q000009:adverse effects*; D000818:Animals; D002452:Cell Count; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006624:Hippocampus / Q000473:pathology*; D007649:Ketamine / Q000627:therapeutic use*; D008012:Lidocaine / Q000009:adverse effects*; D008297:Male; D009474:Neurons / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D008012:Lidocaine