Post-lesion administration of 5-HT1A receptor agonist 8-OH-DPAT protects cholinergic nucleus basalis neurons against NMDA excitotoxicity

Abstract

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.