Tehran University of Medical Sciences Iranian Journal of Psychiatry 1735-4587 5 1 2010 03 15 11 17 Mohammad-Reza Zarrindast Department of Pharmacology, School of Medicine and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran Institute for Studies in Theoretical Physics and Mathematics, School of Cognitive Sciences, Tehran, Iran Institute for Cognitive Science Studies, Tehran, Iran Saba Taheri Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Ameneh Rezayof Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran 2015 10 14 Objective: The nucleus accumbens (NAc) receive histaminergic neurons from tuberomammillary nuclei. There are 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 anxiety-related behaviors. Methods:   Rats   were   anesthetized   with   intra-peritoneal   injection   of ketamine  hydrochloride,  plus  xylazine  and  then   were  placed  in  a stereotaxic  apparatus.  In  addition,  two  stainless-steel  cannuale  were placed 2 mm above the nucleus accumbens shell. Seven days after recovery from surgery, the behavioral testing was started.  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. Results: 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. Conclusion: The results may indicate a modulatory effect for the H1  and H2  histamine receptors of nucleus accumbens in the anxiety behavior of rats. https://ijps.tums.ac.ir/index.php/ijps/article/view/381 https://ijps.tums.ac.ir/index.php/ijps/article/download/381/377