The effect of intrahippocampal injection of orexin A and orexin receptor antagonists 1 and 2 on passive avoidance memory, motor coordination and balance

The aim of the research was to block orexin receptors in the hippocampus and investigate the changes in passive avoidance memory, motor coordination and balance in the absence of orexin effects. The effect of intra-hippocampal injection of the orexin receptor type 2 antagonist JNJ-10397049 on passive avoidance memory, motor coordination and balance was not investigated in previous studies, which we addressed in this research.

Twenty adult male Wistar rats weighing 220-250 grams were randomly divided into four groups. Animals in each group respectively received saline, Orexin A, Orexin A and Orexin receptor type 1 antagonist, or Orexin A and Orexin receptor type 2 antagonist in their hippocampus. Subsequently, passive avoidance memory was evaluated using a shuttle box, while motor coordination and balance were assessed utilizing rotarod devices.

The average delay in entering the dark area and the total time that the animals spent in the light area of the shuttle box increased in the orexin-receiving group compared to the control group. However, these values significantly decreased in the groups that received both orexin and orexin receptor antagonists, in comparison to the group that received orexin alone (p < 0.01).
Furthermore, the duration of motor coordination and balance impairment 30 minutes after injection increased in the orexin-treated group compared to the control group, but it showed a significant decrease (p < 0.01) in the groups that received both orexin and orexin receptor antagonists, when compared to the group that received orexin alone.

It seems that orexin in the hippocampus improves the retrieval of passive avoidance memory, motor coordination and balance. On the other hand, Orexin receptor antagonists disrupt these two processes.
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