Post-lesion administration of 5-HT1A receptor agonist 8-OH-DPAT protects cholinergic nucleus basalis neurons against NMDA excitotoxicity.
Recent evidence indicates that serotonin (5-HT)1A receptor agonists may abrogate excitotoxic brain damage. We investigated whether a single i.p. injection of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), at a dose of 2.5 mg/kg, protects cholinergic neurons of the rat magnocellular nucleus basalis (MBN) against NMDA excitotoxicity when administered at post-injury intervals ranging from 6 to 96 h. Drug effects on passive avoidance learning and on the density of cortical cholinergic innervation, a measure of neuronal survival in the damaged MBN, were analyzed. Our results demonstrate that 8-OH-DPAT, when administered up to 24 h post-lesion, significantly attenuates both behavioral and neuroanatomical consequences of NMDA excitotoxicity on cholinergic MBN neurons; and support the hypothesis that 5-HT1A receptor agonists may interfere with delayed neuronal death in vivo that is of significance in the pharmacological treatment of neurological disorders associated with excitotoxic neuronal damage.
Oosterink
Bart J
BJ
Department of Molecular Neurobiology, Graduate School of Behavioural and Cognitive Neurosciences, University of Groningen, Kerklaan 30, NL-9750 AA Haren, The Netherlands.
Harkany
Tibor
T
Luiten
Paul G M
PG
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000627:therapeutic use*; D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000032:analysis; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D020532:Basal Nucleus of Meynert / Q000187:drug effects*; D002470:Cell Survival; D004334:Drug Administration Schedule; D007267:Injections; D007274:Injections, Intraperitoneal; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013238:Stereotaxic Techniques
D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D016202:N-Methylaspartate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000110:Acetylcholinesterase; D000109:Acetylcholine