BACKGROUND: Ketamine is a noncompetitive antagonist of N-methyl-D-aspartic acid receptor. Some researchers suggest that N-methyl-D-aspartic acid (NMDA) receptor is closely related to epileptic attack. OBJECTIVE: To observe inhibitory effect of ketamine on lighting amygdala of rats and analyze pathway of anti-lighting. DESIGN: Randomized controlled animal study. SETTING: Department of Pharmacology and Department of Management, Pharmacological College of Taishan Medical College; Department of Pharmacology, Medical College of Qingdao University. MATERIALS: Sixty adult female Wistar rats, of clean grade, weighing 180-200 g, were provided by Animal Center of Qingdao Institute of Drug Control. Ketamine hydrochloride was provided by the First Pharmacological Factory of the First Biochemical Pharmacology Company of Shanghai, and nicardipine, an antagonist of calcium ions, was provided by Sigma Company. METHODS: The experiment was completed in the Department of Pharmacology, Medical College of Qingdao University from March to November 2004. ① Model establishing: After anesthesia, left and right amygdalas were inserted with double electrodes. The top was separated about 0.25 mm, and the other end was welded with a micro-plug, respectively. Electrode and micro-plug were fixed with dental base acrylic resin powder at the surface of cranium. Two weeks after recovery, right amygdala was stimulated with constant current once a day. According to Racine technique, attacking intensity was divided into 5 grades: grade I: closing eyes, a little tingling of beards and twitching face; grade Ⅱ: nodding, chewing accompanying with twitching face; grade Ⅲ: raising one of a forelimb and clonus; grade Ⅳ: standing accompanying with bilateral forelimbs; grade Ⅴ: standing accompanying with falling down. Rats with grades Ⅳ and Ⅴ were used to establish secondarily generalized epilepsy. If 3 successive attacks of grade Ⅴ were observed, the lighting was to be successful. ② Effect of ketamine on lighting amygdala of rats: A total of 24 rats were divided into 3 groups with 8 in each group according to lot technique. Rats in the 3 groups were intraperitoneally injected with 30.0, 10.0 and 5.0 mg/kg ketamine, respectively; 30 minutes later, after-discharging value was measured and rats were stimulated with constant current; otherwise, other parameters were not changed. In addition, after-discharging duration and Racine grade were recorded. ③ Effect of ketamine and amygdala on lighting attack of rats: Another 24 rats were divided into 3 groups according to lot technique and intraperitoneally injected with 5.0 mg/kg ketamine, 2 mg/kg nicardipin and 5.0 mg/kg ketamine + 2 mg/kg nicardipin, respectively. The injected volume was 2 mL/kg and after-discharging duration and Racine grade were recorded before and after administration. MAIN OUTCOME MEASURES: Effect of ketamine with various dosages and ketamine + nicardipine with ineffective dosages on after-discharging duration and Racine grade after lighting amygdala. RESULTS: Among 50 rats, 48 with successful lighting amygdale of dpileptic model were involved in the final analysis. ① Effect of ketamine on lighting amygdala of rats: The after-discharging duration was (52.4±16.5) and (28.4±21.4) s after administration and (65.6±10.3), (65.5±13.2) s before administration, and there was significant difference (P < 0.05-0.01); Racine grade was 3.6±1.19 and 2.0±0.99 after administration and 5.0±0 and 5.0±0 before administration, and there was significant difference (P < 0.05-0.01). However, if the injected dosage was 5.0 mg/kg, after-discharging duration and Racine grade were similar before and after administration (P > 0.05). ② Effect of ketamine + nicardipine on lighting attack: When rats were injected with 5 mg/kg ketamine or 2 mg/kg nicardipine, respectively, after-discharging duration was (63.8±11.7), (63.0±35.3) s before administration and (63.6±12.5), (59.8±38.8) s after administration, and there was no significant difference (P > 0.05). Meanwhile, Racine grade was 4.6±0.5 and 5.0±0 before administration and 5.0±0 and 5.0±0 after administration, and there was no significant difference (P > 0.05). When rats were injected with 5.0 mg/kg ketamine + 2.0 mg/kg nicardipine, after-discharging duration and Racine grade were (42.3±9.7) s and 3.1±0.7, respectively, and these were obviously shorter/lower than those before administration [(60.6±10.3) s, 5.0±0, P < 0.05]. CONCLUSION: Ketamine (10 and 30 mg/kg) can inhibit lighting attack of amygdale in epilepsy, but low dosage (5 mg/kg) was ineffective; however, the combination of 5.0 mg/kg ketamine and 2 mg/kg nicardipin can also inhibit lighting. Therefore, it is suspected that effect of ketamine on anti-lighting is reacted on inhibiting Ca2+ internal flow mediated by NMDA receptor.
