The 5-HT1A receptor agonist Bay X 3702 inhibits apoptosis induced by serumdeprivation in cultured neurons

We examined whether the highly selective 5-HT1A receptor agonist (-)-(R)-2- [4-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl] amino]butyl]-11,2-benz-isoth iazol-3(2H)-one I,l-dioxide monohydrochloride (Bay x 3702) could inhibit ne uronal apoptosis induced by serum deprivation. In primary cultures of chick embryonic neurons and in mixed neuronal/glial cultures from neonatal rat h ippocampus, Bay x 3702 (1 mu M) rescued serum-deprived neurons from apoptos is. The antiapoptotic effect of Bay x 3702 (1 mu M) was blocked in chick ne urons by the selective 5-MT1A receptor antagonists 4-iodo-N-[2-[4-(methoxyp henyl)-1-piperazin]ethyl]-N-2-pylidinyl-benzamide hydrochloride (p-MPPI, 10 mu M) and 4-[3-benzotriazol-1-propyl]-1-(2-methoxyphenyl)-piperazine (BPMP , 10 mu M) as well as by anti-nerve growth factor (anti-NGF) antibodies and in rat neurons by N-[2-[4-(9-methoxy)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane-carboxamide trihydrochloride (WAY 100635, 10 mu M). We found on ly under control conditions (medium with serum), but not in serum-deprived cultures, that NGF secretion was 6-fold increased by Bay x 3702 (1 mu M) co mpared to untreated cultures. Additionally, Bay x 3702 (4 mu g/kg i.v.), in fused within a period of 4 h, significantly increased the NGF content of th e rat hippocampus, but not of the striatum. In summary, our data suggest th at Bay x 3702 inhibited growth factor withdrawal-induced apoptosis by the s timulation of 5-HT1A receptors and that the NGF signalling pathway is invol ved in the mechanism of action. (C) 1999 Elsevier Science B.V. All rights r eserved.