The effects of ethanol and the serotonin1A agonist ipsapirone on the expression of the serotonin1A receptor and several antiapoptotic proteins in fetal rhombencephalic neurons

Previously, this laboratory demonstrated that ethanol reduces the number of developing serotonin (5-HT)-containing neurons by increasing apoptosis. We also found that 5-HT1A agonists attenuate the proapoptotic effects of ethanol and the ethanol-mediated reduction of fetal 5-HT neurons. These neuroprotective effects are mediated in part by the ability of 5-HT1A agonists to activate the phosphatidyl 3′-kinase (PI-3K) prosurvival pathway. NF-κB is one of the downstream effectors activated by this pathway. In the present study, we used quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to determine the effects of 50 mM ethanol and 100 nM of ipsapirone, a 5-HT1A agonist, on the expression of several NF-κB-dependent antiapoptotic genes: X-linked inhibitor of apoptosis protein (XIAP), cIAP1, cIAP2, Bcl-2, and Bcl-xl. We also investigated the effects of ethanol and ipsapirone on the expression of the gene encoding the 5-HT1A receptor. The results demonstrate that ethanol reduces the expression of several prosurvival genes: XIAP, cIAP1, cIAP2, Bcl-2, and Bcl-xl. Importantly, the ethanol-mediated reduction in the expression of XIAP and Bcl-xl was prevented by co-treatment with ipsapirone. Thus, the damaging effects of ethanol are likely to involve a reduction in several prosurvival proteins. Moreover, the protective effects of ipsapirone on ethanol-treated neurons might involve their ability to prevent the reduction of XIAP and Bcl-xl. Although ipsapirone treatment decreased the expression of cIAP1, Bcl-2, and Bcl-xl in control neurons, our prior studies suggest that their survival is not reduced by ipsapirone. We also observed an increased expression of the 5-HT1A receptor in ipsapirone-treated control neurons.