Neuroprotection against N-methyl-D-aspartate-induced excitotoxicity in rat magnocellular nucleus basalis by the 5-HT(1A) receptor agonist 8-OH-DPAT

Bart J. Oosterink, S. Mechiel Korte, C. Nyakas, Jakob Korf, Paul G M Luiten

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The present study reports the neuroprotective efficacy of the 5-HT(1A) receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and ipsapirone against in vivo excitotoxic neuronal injury. Excitotoxic cell death was induced by injections of N-methyl-d-aspartate (NMDA) in the rat magnocellular nucleus basalis. The neurodegenerative effects were quantified by image analysis of the axonal density of the nucleus basalis projection to the somatosensory cortex visualized with acetylcholinesterase histochemistry. Pretreatment with 8-OH-DPAT-but not ipsapirone-1 h prior to NMDA infusion showed significant preservation of cortical cholinergic innervation in all doses tested. Furthermore, 8-OH-DPAT exhibited sustained efficacy under homeothermic conditions in which the body temperature was maintained at 36.8±0.1°C. These data indicate that selective 5-HT(1A) receptor activation by 8-OH-DPAT protects against NMDA-induced excitotoxic neuronal damage, probably as a result of 5-HT(1A) receptor-mediated neuronal hyperpolarization. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)147-152
Number of pages6
JournalEuropean Journal of Pharmacology
Volume358
Issue number2
DOIs
Publication statusPublished - Oct 2 1998

Fingerprint

8-Hydroxy-2-(di-n-propylamino)tetralin
Receptor, Serotonin, 5-HT1A
N-Methylaspartate
Aspartic Acid
Somatosensory Cortex
Acetylcholinesterase
Body Temperature
Cholinergic Agents
Cell Death
Neuroprotection
hydroxide ion
Injections
Wounds and Injuries

Keywords

  • 5-HT(1A) receptor
  • 8-OH-DPAT
  • Excitotoxicity
  • Homeothermic condition
  • Neuroprotection
  • NMDA (N-methyl-D-aspartate)

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Neuroprotection against N-methyl-D-aspartate-induced excitotoxicity in rat magnocellular nucleus basalis by the 5-HT(1A) receptor agonist 8-OH-DPAT. / Oosterink, Bart J.; Mechiel Korte, S.; Nyakas, C.; Korf, Jakob; Luiten, Paul G M.

In: European Journal of Pharmacology, Vol. 358, No. 2, 02.10.1998, p. 147-152.

Research output: Contribution to journalArticle

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abstract = "The present study reports the neuroprotective efficacy of the 5-HT(1A) receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and ipsapirone against in vivo excitotoxic neuronal injury. Excitotoxic cell death was induced by injections of N-methyl-d-aspartate (NMDA) in the rat magnocellular nucleus basalis. The neurodegenerative effects were quantified by image analysis of the axonal density of the nucleus basalis projection to the somatosensory cortex visualized with acetylcholinesterase histochemistry. Pretreatment with 8-OH-DPAT-but not ipsapirone-1 h prior to NMDA infusion showed significant preservation of cortical cholinergic innervation in all doses tested. Furthermore, 8-OH-DPAT exhibited sustained efficacy under homeothermic conditions in which the body temperature was maintained at 36.8±0.1°C. These data indicate that selective 5-HT(1A) receptor activation by 8-OH-DPAT protects against NMDA-induced excitotoxic neuronal damage, probably as a result of 5-HT(1A) receptor-mediated neuronal hyperpolarization. Copyright (C) 1998 Elsevier Science B.V.",
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