Orexin-2 receptor antagonism in the cornu ammonis 1 region of hippocampus prevented the antinociceptive responses induced by chemical stimulation of the lateral hypothalamus in the animal model of persistent pain

Orexins are excitatory neuropeptides, mainly produced by neurons located in the lateral hypothalamus, which project to many brain areas. The orexinergic system plays a fundamental role in arousal, sleep/wakefulness, feeding, energy homeostasis, motivation, reward, stress and pain modulation. As a prominent part of the limbic system, the hippocampus has been involved in formalin-induced nociception modulation. Moreover, hippocampus regions express both orexin-1 (OX1) and orexin-2 (OX2) receptors. The present study investigated the role of OX2 receptors (OX2R) within the cornu ammonis 1 (CA1) region of the hippocampus in the mediation of lateral hypothalamus-induced antinociception. Fifty-three male Wistar rats were unilaterally implanted with two separate cannulae into the lateral hypothalamus and CA1. Animals were pretreated with intra-CA1 TCS OX2 29 as an OX2R antagonist before intra-lateral hypothalamus administration of carbachol (250 nM) as a muscarinic agonist for chemical stimulation of orexinergic neurons. Formalin test was used as an animal model of persistent pain, following intra-lateral hypothalamus carbachol microinjection. Results showed that the chemical stimulation of the lateral hypothalamus significantly attenuated formalin-evoked nociceptive behaviors during both phases of the formalin test, and administration of TCS OX2 29 into the CA1 blocked these antinociceptive responses in both phases, especially in the late phase. These findings suggest that OX2 receptors in the CA1 partially mediate the lateral hypothalamus-induced antinociceptive responses in persistent inflammatory pai

A New Device for Step-Down Inhibitory Avoidance Task—Effects of Low and High Frequency in a Novel Device for Passive Inhibitory Avoidance Task That Avoids Bioimpedance Variations

Step-down inhibitory avoidance task has been widely used to evaluate aversive memory, but crucial parameters inherent to traditional devices that may influence the behavior analysis (as stimulus frequency, animal's bioimpedance) are frequently neglected.We developed a new device for step-down inhibitory avoidance task by modifying the shape and distribution of the stainless steel bars in the box floor where the stimuli are applied. The bars are 2 mm wide, with rectangular shape, arranged in pairs at intervals of 1cm from the next pairs. Each pair makes an electrical dipole where the polarity inverts after each pulse. This device also presents a component that acquires and records the exact current received by the animal foot and precisely controls the frequency of stimulus applied during the entire experiment.Different from conventional devices, this new apparatus increases the contact surface with bars and animal's paws, allowing the electric current pass through the animal's paws only, drastically reducing the influence of animal's bioimpedance. The analysis of recorded data showed that the current received by the animal was practically the same as applied, independent of the animal's body composition. Importantly, the aversive memory was observed at specific stimuli intensity and frequency (0.35 or 0.5 mA at 62 and 125 Hz but not at 0.20 mA or 20 Hz). Moreover, with this device it was possible to observe the well-known step-down inhibitory avoidance task memory impairment induced by guanosine.This new device offers a substantial improvement for behavioral analysis in step-down inhibitory avoidance task and allows us to precisely compare data from different animals with distinct body composition