Skip to main content
SpringerLink
Log in

Effects of ketanserin and mianserin on delayed neuronal death induced by cerebral ischemia in Mongolian gerbils

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

We examined whether ketanserin and mianserin, drugs with 5-HT2 receptor antagonistic effects, would have protective effects in Mongolian gerbils on delayed neuronal death induced by cerebral ischemia. When training and test sessions in the passive avoidance task were carried out 6 and 7 days after 3 min of ischemia, passive avoidance impairment was apparent. Destruction and disappearance was apparent in the hippocampal CA1 neurons at 7 days after the induced ischemia. Administration of ketanserin (5–20 mg/kg) and mianserin (5–20 mg/kg) led to better passive avoidance and prevented the delayed neuronal death induced by the ischemia. These effects of ketanserin and mianserin were not inhibited by treatment with the cholinergic blocker scopolamine (5 mg/kg). Thus, ketanserin and mianserin have a protective effect on delayed neuronal death in gerbils and the effects of these drugs are not mediated by serotonergic and cholinergic systems.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Araki H, Nojiri M, Kimura M, Aihara H (1987) Effect of minaprine on “delayed neuronal death” in Mongolian gerbils with occluded common carotid arteries. J Pharmacol Exp Ther 242:686–691

    PubMed  Google Scholar 

  • Araki H, Uchiyama-Tsuyuki Y, Karasawa Y, Aihara H (1989) Effect of minaprine on changes in monoamine contents in Mongolian gerbils with 5-min occlusion of common carotid arteries. Jpn J Pharmacol 50:445–453

    PubMed  Google Scholar 

  • Bentue'-Ferrer D, Raymann JM, Bagot H, Drissche VD, Certaines JD, Allain H (1986) Aminergic neurotransmitter and water content changes in rats after transient forebrain ischemia. J Neurochem 47:1672–1677

    PubMed  Google Scholar 

  • Bjorklund A, Hokfelt T, Swanson Lw (1987) Integrated systems of the CNS, part I hypothalamus, hippocampus, amygdala, retina. Handbook of chemical neuroanatomy, 5. Elsevier, Amsterdam, pp 208–211

    Google Scholar 

  • Brown CM, Kilpatrick AT, Martin A, Spedding M (1988) Cerebral ischemia reduces the density of 5-HT2 binding sites in the frontal cortex of the gerbil. Neuropharmacology 27:831–836

    Article  PubMed  Google Scholar 

  • Fujikura H, Kato H, Nakano S, Kogure K (1989) A serotonin S2 antagonist, naftidrofuryl, exhibited a protective effect on ischemic neuronal damage in the gerbil. Brain Res 494:387–390

    Article  PubMed  Google Scholar 

  • Gustafson I, Westerberg E, Wieloch (1990) Protection against ischemia-induced neuronal damage by the α2-adrenoceptor antagonist idazoxan: influence of time of administration and possible mechanisms of action. J Cereb Blood Flow Metab 10:885–894

    PubMed  Google Scholar 

  • Iijima S, Hara K, Suga H, Nakamura S, Kameyama M (1986) Effect of ischemia on the hydroxylase cofactor (tetrahydrobiopterin) and monoamine neurotransmitters in rat brain. Stroke 17:529–533

    PubMed  Google Scholar 

  • Ito U, Spatz M, Walker JT, Klatzo I (1975) Experimental cerebral ischemia in Mongolian gerbils. Acta Neuropathol 32:209–223

    Article  PubMed  Google Scholar 

  • Janssen PAJ (1981) The pharmacology of specific, pure and potent serotonin 5-HT2 or S2-antagonists. Eighth International Congress of Pharmacology, Tokyo (Japan), July 19–24

  • Karasawa Y, Araki H, Okuyama S, Aihara H, Otomo S (1990) Effect of minaprine and other reference drugs on passive avoidance impairment induced by cerebral ischemia in Mongolian gerbils. Jpn J Pharmacol 53:339–346

    PubMed  Google Scholar 

  • Karasawa Y, Araki H, Otomo S (1992) Cholinomimetic activity of minaprine is related to the amelioration of delayed neuronal death in gerbils. Physiol Behav 52:141–147

    Article  PubMed  Google Scholar 

  • Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69

    Article  PubMed  Google Scholar 

  • Kirino T, Sano K (1984a) Selective vulnerability in the gerbil hippocampus following transient ischemia. Acta Neuropathol 62:201–208

    Article  Google Scholar 

  • Kirino T, Sano K (1984b) Fine structural nature of delayed neuronal death following ischemia in the gerbil hippocampus. Acta Neuropathol 62:209–218

    Article  PubMed  Google Scholar 

  • Leysen JE, Awouters F, Kennis L, Laduron PM, Vandenberk J, Janssen PAJ (1981) Receptor binding profile of R 41,468, a novel antagonist at 5-HT2 receptors. Life Sci 28:1015–1022

    Article  PubMed  Google Scholar 

  • Leysen JE, Gommeren W, Gompel PV, Wynants J, Janssen PFM, Laduron. PM (1985) Receptor-binding properties in vitro and in vivo of ritanserin. A very potent and long acting serotonin-S2 antagonist. Mol Pharmacol 27:600–611

    PubMed  Google Scholar 

  • Matsumoto M, Kimura K, Fujisawa A, Matsuyama T, Fukunaga R, Yoneda S, Wada H, Abe H (1984) Differential effect of cerebral ischemia on the monoamine content of discrete brain regions of the Mongolian gerbil(Meriones unguiculatus). J Neurochem 42:647–651

    PubMed  Google Scholar 

  • McCall RB, Aghajanian GK (1979) Serotonergic facilitation of facial motoneuron excitation. Brain Res 169:11–27

    Article  PubMed  Google Scholar 

  • Mitani A, Andou Y, Masuda S, Kataoka K (1991) Transient forebrain ischemia of three-minute duration consistently induces severe neuronal damage in field CA1 of the hippocampus in the normothermic gerbil. Neurosci Lett 131:171–174

    Article  PubMed  Google Scholar 

  • Muramatsu M, Tamaki-Ohashi J, Usuki C, Araki H, Aihara H (1988) Serotonin-2 receptor-mediated regulation of release of acetylcholine by minaprine in cholinergic nerve terminal of hippocampus of the rat. Neuropharmacology 27:603–609

    Article  PubMed  Google Scholar 

  • Nishino K, Davis JN (1989) Rapid reduction in [3H]prazosin binding to gerbil forebrain membranes during bilateral common carotid artery occlusion. J Cereb Blood Flow Metab 9:358–363

    PubMed  Google Scholar 

  • Olney JW (1969) Brain lesions, obesity and other disturbances in mice treated with monosodium glutamate. Science 164:719–721

    PubMed  Google Scholar 

  • Onodera H, Sato G, Kogure K (1986) Lesions to Schaffer collaterals prevent ischemic death of CA1 pyramidal cells. Neurosci Lett 68:169–174

    Article  PubMed  Google Scholar 

  • Peroutka SJ, Snyder SH (1981) [3H]mianserin: differential labeling of serotonin2 and histamine1 receptors in rat brain. J Pharmacol Exp Ther 216:142–148

    PubMed  Google Scholar 

  • Prehn JHM, Backhauß C, Karkoutly C, Nuglisch J, Peruche B, Roberg C, Krieglstein J (1991) Neuroprotective properties of 5-HT1A receptor agonists in rodent models of focal and global cerebral ischemia. Eur J Pharmacol 203:213–222

    Article  PubMed  Google Scholar 

  • Rothman SM (1984) Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J Neurosci 4:1884–1891

    PubMed  Google Scholar 

  • Segawa T (1990) Multiple 5-HT receptors. Jpn J Neuropsychopharmacol 13:21–26

    Google Scholar 

  • Tang SW, Serman P (1980) Effect of antidepressant drugs on serotonergic and adrenergic receptors. Naunyn-Schmiedeberg's Arch Pharmacol 311:255–261

    Article  Google Scholar 

  • Uchiyama-Tsuyuki Y, Araki H, Karasawa Y, Aihara H (1989) Changes in monoamine contents in the brains of Mongolian gerbils following a 5-min occlusion of the bilateral carotid arteries. Jpn J Pharmacol 50:357–361

    PubMed  Google Scholar 

  • Welch KMA, Chabi E, Buckingham J, Bergin B, Achar VS, Meyer JS (1977) Catecholamine and 5-hydroxytryptamine levels in ischemic brain: influence ofp-chlorophenylalanine. Stroke 8:341–346

    PubMed  Google Scholar 

  • Wurtmann RJ, Lavyne M, Maskowitz M, Zervus NT (1977) Brain monoamine neurotransmitters and the pathophysiology of stroke. In: Owman C, Edvinsson L (eds) Neurogenic control of the brain circulation. Pergamon Press, Oxford, pp 483–495

    Google Scholar 

  • Zervus NT, Lavyne MH, Negaro M (1975) Neurotransmitters and the normal and ischemic cerebral circulation. N Engl J Med 293:812–816

    PubMed  Google Scholar 

  • Zivin JA, Venditto JA (1984) Experimental CNS ischemia: serotonin antagonists reduce or prevent damage. Neurology 34:469–474

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Research Center, Taisho Pharmaceutical, Yoshino-cho 1-403, Ohmiya, 330, Saitama, Japan

    Yasuko Karasawa, Hiroaki Araki & Susumu Otomo

Authors
  1. Yasuko Karasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroaki Araki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susumu Otomo
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karasawa, Y., Araki, H. & Otomo, S. Effects of ketanserin and mianserin on delayed neuronal death induced by cerebral ischemia in Mongolian gerbils. Psychopharmacology 109, 264–270 (1992). https://doi.org/10.1007/BF02245872

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245872

Key words

Search

Navigation