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Lee HJ, Ban JY, Cho SO, Seong YH: Stimulation of 5-HT1A receptor with 8-OH-DPAT inhibits hydrogen peroxide-induced neurotoxicity in cultured rat cortical cells. Pharmacol Res. 2005 Mar;51(3):261-8.
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. |
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