Behavioral effects of orexin-A in the bed nucleus of stria terminalis of rat

Lateral hypothalamic orexin expressing neurons send fibers to various brain areas such as the brainstem, hypothalamus, cortex and limbic system, including the amygdala and the bed nucleus of stria terminalis (BST). The role of orexins in reward seeking, response to stress, learning and memory have recently been investigated. BST is known to be involved in the regulation of hormonal and behavioral responses to stress, anxiety and sexual behavior. The present study aimed to elucidate the involvement of orexin-A (OXA) in learning, anxiety and reinforcement processes in the BST. Bilateral OXA microinjections in the doses of 250 ng (70 pmol) and 500 ng (140 pmol) into the BST of male Wistar rats were performed 30 min prior to open field (OPF), elevated plus maze (EPM), conditioned place preference (CPP), or passive avoidance (PAV) tests. In the CPP, 250 ng OXA increased the number of entering into the treatment quadrant. The 500 ng OXA had significant anxiolytic effects on EPM. There was a mild increase in the locomotor activity in the OPF as well as in the EPM. In the PAV, OXA dose-dependently reduced the retention time to enter the dark room, indicating its suppressive effect on avoidance learning. Our findings reveal that OXA shows functional heterogeneity in learning and memory processes having a specific role in the modulation of PAV learning. The inhibition on avoidance learning is supposed to be due to the anxiolytic effect of OXA.