The Effects of Histaminergic Agents in the Nucleus Accumbens of Rats in the Elevated Plus-Maze Test of Anxiety

Introduction/ The nucleus accumbens (NAc) receives histaminergic neurons from tuberomammillary nuclei. There are also reports indicating that central histamine systems are involved in many physiological behavioral processes, including anxiety. The aim of the present study was to assess whether the histaminergic system of the NAc is involved in the anxiety-related behaviors. As a model of anxiety the elevated plus maze which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents was used in male Wistar rats. Intra-NAc administration of histamine (0.01, 0.1 and 1 μg/rat) increased the percentage of open arm time (%OAT) and open arm entries (%OAE) but not locomotor activity, indicating an anxiolytic response. Furthermore, bilateral microinjections of different doses of the H1 receptor antagonist pyrilamine (0.001, 0.01, 0.1 and 1 μg/rat) or the H2 receptor antagonist ranitidine (0.001, 0.01, 0.1 and 1 μg/rat) into the NAc increased %OAT and %OAE but not locomotor activity. However, both histamine and histamine receptor antagonists showed an anxiolytic-like effect, the antagonists (1 μg/rat) also decreased the histamine response. The results may indicate a modulatory effect for the H1 and H2 histamine receptors of nucleus accumbens in the anxiety behavior of rats.