Interaction between dorso-hyppocampal histaminergic and medio-septal opioidergic systems in anxiety behavior

Authors

University of Mazandaran, Babolsar

Abstract
Septohippocampal system plays an important role in regulating fear and anxiety behaviors. In this study, the effects of histamine injected into the dorsal hippocampus and opioidergic agents into medial septum on the anxiety-like behaviors in rats were analyzed, using the Elevated Plus-Maze (EPM) test. Injection of 1 and 5 μg/rat histamine into dorsal hippocampus had no effect on anxiety-like behavior, while injection of 10 μg/rat histamine increased the percentage of open arm time (%OAT) and open arm entry (%OAE), which indicated the anxiolytic effects of histamine. Microinjection of morphine, μ-opioid receptor agonist, into the medial septum (1μg/rat) increased the (%OAT) and (%OAE). Doses of 0.25, 0.5 μg/rat morphine had no effect on anxiety. Co-administration of histamine ineffective dose (1μg/rat) to the dorsal hippocampus and ineffective dose of morphine (0.25µg/rat) to the medial septum increased the (%OAT) and (%OAE). Subsequently, injection of different doses of naloxone (1, 2, 4 µg/rat), as an opioid receptor antagonist, into the medial septum in the presence and absence of an effective dose of histamine (10 µg/rat) in the dorsal hippocampus, was studied. Injection of naloxone (4 µg/rat) into medial septum decreased the (%OAT) and (%OAE), but did not alter the locomotor activity, which indicated the anxiogenic effects of naloxone. Simultaneous injection of histamine (10 µg/rat) into dorsal hippocampus with doses of naloxone (1, 2, 4 µg/rat) into the medial septum, indicate anxiolytic effects and increased %OAT and %OAE in Elevated Plus Maze, although when the dose of naloxone was 4μg/rat, this effect was less observed. The results indicate that hippocampus histaminergic system interact with medial septum opioidergic system and the interaction of these systems modulates anxiety behavior.

Keywords


Bartoletti, M., Gaiardi, M., Gubellini, C., Bacchi, A. and Babbini, M. 1990. Morphine attenuation of a conditioned emotional response in postdependent rats. – Eur. J. Pharmacol. 185: 163-167.
Degroot, A. and Kashluba, S. 2001. Septal GABAergic and hippocampal cholinergic systems modulate anxiety in the plus-maze and shock-probe tests. – Pharmacol. Biochem. Behav. 69: 391-399.
DeVries, A.C., Taymans, S.E., Sundstrom, J.M. and Pert, A. 1998. Conditioned release of corticosterone by contextual stimuli associated with cocaine is mediated by corticotropin-releasing factor. – Brain Res. 786: 39-46.
Drugan, R.C. and Skolnick, P. 1986. Low doses of muscimol produce anticonflict actions in lateral septum of the rat. – Neuropharm. 25: 203-205.
Eriksson, K.S., Stevens, D.R. and Haas, H.L. 2000. Opposite modulation of histaminergic neurons by nociceptin and morphine. – Neuropharm. 39: 2492-2498.
Filliol, D., Ghozland, S., Chluba, J., Martin, M., Matthes, H.W. and Simonin, F. 2000. Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. – Nat. Genet. 25: 195-200.
Frisch, C., Hasenohrl, R.U., Krauth, J. and Huston, J.P. 1998. Anxiolytic-like behavior after lesion of the tuberomammillary nucleus E2-region. – Exp. Brain Res. 119: 260-264.
Gazyakan, E., Disko, U., Haaf, A., Heimrich, B. and Jackisch, R. 2000. Postnatal development of opioid receptors modulating acetylcholine release in hippocampus and septum of the rat. – Dev. Brain Res. 123: 135-141.
Givens, B.S. and Olten, D.S. 1990. Cholinergic and Gabaergic modulation of medial septal area: effect on working memory. – Behave. Neurosci. 104: 849-855.
Gorden, M.S. 2000. Neurobiology. Third editon. – Oxford University Press. 34- 618 pp.
Hough, L.B., Nalwalk, J.W., Barnes, W.G., Leurs, R., Menge, W.M., Timmerman H. and Wentland, M. 2000. A third life for burimamide. Discovery and characterization of a novel class of non-opioid analgesics derived from histamine antagonists. – Ann. NY Acad. Sci. 909: 25-40.
Kõks, S., Soosaar, A., Võikar, V., Bourin, M. and Vasar, E. 1999. BOC-CCK-4, CCK (B) receptor agonist, antagonizes anxiolytic-like action of morphine in elevated plus-maze. – Neuropeptides 33: 63-69.
Lamour, Y., Bassant, M.H., Jobert, A. and Joly, M. 1989. Septo-hippocampal neurons in the aged rat: relation between their electrophysiological and pharmacological properties and behavioral performances. – Neurobiol. Aging. 10: 181-186.
Mizumori, S.J.Y., Ward, K.E. and Lavoie, A.M. 1992. Medial septal modulation of entorhinal single unit activityin anesthetized and freely moving rat. – Brain Res. 570: 188-197.
Moghaddam, B. 2003. Bringing order to the glutamate chaos in schizophrenia. – Neuron 40: 881-884.
Nobre, M.J., Ribeiro, D.S.N., Aguiar, M.S. and Brandao, M.L. 2000. Blockade of ‌and activation of ‌opioid receptors in the dorsal periaqueductal gray matter produce defensive behavior in rats in the elevated plus-maze. – Eur. J. Pharmacol. 404: 145-151.
Panula, P., Yang, H.P. and Costa, E. 1984. Histamine-containing neurons in the rat hypothalamus. – Proc. Natl. Acad. Sci. USA. 81: 2572-2576.
Paxinos, G. and Watson, C. 1998. The rat brain in stereotaxic coordinates. – Accademic Press. New York: USA. 28-31 pp.
Pesold, C. and Treit, D. 1994. The septum and amygdala differentially mediate the anxiolytic effects of benzodiazepines. – Brain Res. 638: 295- 301.
Rostami, P., Hajizadeh-Moghaddam, A. and Zarrindast, M.R. 2006. The effects of histaminergic agents in the ventral hippocampus of rats in the plus-maze test of anxiety-like behaviors. – Physiol. Behavior. 87: 891-896.
Santos, N.R., Huston, J.P. and Brandao, M.L. 2003. Blockade of histamine H2 receptors of the periaqueductal gray and inferior colliculus induces fearlike behaviors. – Pharmacol. Biochem. Behav. 75: 25-33.
Shin, I.C., Kirn, H.C., Swanson, J., Hong, J.T. and Oh, K.W. 2003. Anxio-lyic effects of acute morphine can be modulate by nitric oxide systems. – Pharmacol. 68: 183-189.
Swanson L.W. and Cowan W.M. 1979. The connections of the septal region in the rat. – J. Comp. Neurol. 186: 621- 656.
Tanaka M., Yoshida, M., Emoto, H. and Ishii, H. 2000. Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: basic studies. – Eur. J. Pharmacol. 405: 397-406.
Tsuda, M., Suzuki, T., Misawa, M. and Nagase, H. 1996. Involvement of the opioid system in the anxiolytic effect of diazepam in mice. – Eur. J. Pharmacol. 307: 7-14.
Yamatodani, A., Fukuda, H., Wada, H., Iwaeda, T. and Watanabe, T. 1985. High-performance liquid chromatographic determination of plasma and brain histamine without previous purification of biological samples: cation-exchange chromatography coupled with post-column derivatization fluorometry. – J. Chromatogr. 8: 115-23.
Zarrindast, M.R., Torabi, M., Rostami, P. and Fazli-Tabaei, S. 2006. The Effects of histaminergic agents in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety. – Pharmacol. Biochem. Behav. 85: 500-506.
Zarrindast, M.R., Valizadegan, F., Rostami, P. and Rezayof, A. 2006. Histaminergic receptors of medial septum and conditioned place preference: D1 dopamine receptor mechanism. – Brain Res. 1109: 108-116.
Zhang, H.T., Xu, Z.M., Luo, Z.P. and Qin, B.Y. 1996. Anxiogenic effect of naltrexone in socialinteraction test in rats. – Zhongguo Yao Li Xue Bao.17: 314-317.
Volume 4, Issue 2 - Serial Number 12
Summer 2017
Pages 189-200

  • Receive Date 08 June 2026
  • Publish Date 08 June 2026