title: Stimulation of 5-HT1A receptor with 8-OH-DPAT inhibits hydrogen peroxide-induced neurotoxicity in cultured rat cortical cells.
abstract: We investigated the effect of 8-hydroxy-2-(N,N-dipropylamino)tetralin (8-OH-DPAT), a specific 5-HT(1A) receptor agonist, on H(2)O(2)-induced neuronal cell death in cultured rat cortical cells. H(2)O(2) produced a concentration-dependent reduction of cell viability, which was significantly reduced by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801), an N-methyl-d-aspartate (NMDA) receptor antagonist. Pretreatment of 8-OH-DPAT over the concentration range of 1-100 microM significantly inhibited the H(2)O(2) (100 microM)-induced neuronal cell death as assessed by a MTT assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. The protective effect of 8-OH-DPAT (100 microM) was completely blocked by the simultaneous treatment of 1-(2-methoxyphenyl)-4-[4-(2-phthalimideo)butyl]piperazine (NAN-190, 10muM), a selective 5-HT(1A) receptor antagonist, but not in the presence of the dopamine receptor blocker spiperone (10 microM), indicating that the protective effect of 8-OH-DPAT was mediated via 5-HT(1A) receptors. In addition, 8-OH-DPAT inhibited the H(2)O(2)-induced elevation of glutamate release into the medium and cytosolic Ca(2+) concentration ([Ca(2+)](c)), generation of reactive oxygen species (ROS), and caspase-3 activity. These results suggest that the activation of 5-HT(1A) receptor with 8-OH-DPAT may ameliorate an oxydative stress-induced apoptosis of neuronal cell by interfering with the increase of [Ca(2+)](c), and then by inhibiting glutamate release, generation of ROS and caspase activity.
authors.affiliation: College of Veterinary Medicine and Research, Institute of Veterinary Medicine, Chungbuk National University, San 48, Gaesin-dong, Heungduk-Gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Ban
authors.forename: Soon Ock
authors.initials: SO
authors.lastname: Cho
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Seong
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism* / Q000502:physiology; D058825:Serotonin 5-HT1 Receptor Agonists
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006861:Hydrogen Peroxide