Neuroprotection against N-methyl-D-aspartate-induced excitotoxicity in rat magnocellular nucleus basalis by the 5-HT1A receptor agonist 8-OH-DPAT.
The present study reports the neuroprotective efficacy of the 5-HT1A 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 degrees C. These data indicate that selective 5-HT1A receptor activation by 8-OH-DPAT protects against NMDA-induced excitotoxic neuronal damage, probably as a result of 5-HT1A receptor-mediated neuronal hyperpolarization.
Oosterink
B J
BJ
Department of Animal Physiology, Graduate School of Behavioral and Cognitive Neuroscience, University of Groningen, Haren, The Netherlands. b.j.oosterink@biol.rug.nl
Korte
S M
SM
Nyakas
C
C
Korf
J
J
Luiten
P G
PG
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013377:Substantia Innominata / Q000187:drug effects*
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D016202:N-Methylaspartate; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000110:Acetylcholinesterase