engleski

The influence of calcium channel blockers nimodipine, nifedipine and amlodipine on passive avoidance in hypoxia exposed rats

Cerebral hypoxia causes various functional disturbances and damage of neurons in central nervous system. Among the theories to explain neuronal damage due to hypoxia, one of the most widely considered is the intracellular accumulation of calcium ions. One of the major mechanisms for regulating calcium entry into the cells is through the 'L' type of voltage sensitive calcium channels. These channels can be modulated by various drugs that have been claimed to counteract the disturbances in calcium homeostasis and prevent massive influx of calcium ions. Among them dihydropyridines (DHP) are considered as the most potent. Therefore, the purpose of this study was to investigate the effects of various types of DHP on passive avoidance in hypoxia exposed rats. The study was carried out on Hannover Wistar rats weighing 250 g. The passive avoidance task was performed according to the modified procedure of Jarvik and Kopp (1967). On the first training day the rats were trained to escape the punishment in step-through passive avoidance task. Immediately after the training trial the animals were subjected to a period of oxygen deprivation hypoxia. Passive avoidance retention was tested twenty-four hours later. The behaviour in hypoxia exposed rats under the influence of drugs was measured. The control animals received vehicle solution and others were pretreated with various doses (0.03 ; 0.1, 0.3 ; 1.0 mg/kg) of nimodipine, nifedipine and amlodipine, intra peritoneally, 30 minutes before the first day training session. The results of our experiments show that hypoxia strongly impaired the passive avoidance behaviour in the rat. Namely, retest latencies in hypoxia exposed rats were significantly lower than those of the control animals. Nimodipine, nifedipine and amlodipine administration increased the passive avoidance in hypoxia exposed rats. Statistically significant effects were produced by all tested doses of nimodipine and amlodipine and by nifedipine with doses of 0.1 ; 0.3 and 1.0 mg/kg. It has also been found that the effects of nimodipine were dose dependent.

hypoxia; passive avoidance; nimodipine; nifedipine; amlodipine; rat

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