The serotonin-1A agonist ipsapirone prevents ethanol-associated death of total rhombencephalic neurons and prevents the reduction of fetal serotonin neurons

• Published in: Brain research. Developmental brain research 2004-06, Vol.150 (2), p.79-88
• Main Authors: Druse, Mary J, Tajuddin, Nuzhath F, Gillespie, Roberta A, Dickson, Elizabeth, Atieh, Mohammed, Pietrzak, Constance A, Le, Phong T
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Apoptosis; Cell Death - drug effects; Cell Survival - drug effects; Cells, Cultured; Central Nervous System Depressants - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Embryo, Mammalian; Ethanol - pharmacology; Female; Immunohistochemistry - methods; In Situ Nick-End Labeling - methods; Neurons - drug effects; Neurons - metabolism; Neuroprotective; Pregnancy; Pyrimidines - pharmacology; Rats; Rats, Sprague-Dawley; Rhombencephalon - cytology; Serotonin; Serotonin - metabolism; Serotonin Receptor Agonists - pharmacology; Serotonin-1A receptor agonist; Time Factors
• ISSN: 0165-3806
• DOI: 10.1016/j.devbrainres.2004.02.009

Previously, this laboratory showed that in utero and in vitro ethanol exposure significantly reduces developing serotonin (5-HT) neurons and that treatment with a 5-HT 1A agonist such as buspirone or ipsapirone prevents the ethanol-associated loss. The present study investigated whether ethanol decreases fetal rhombencephalic neurons, including 5-HT neurons, by causing apoptosis. We also investigated whether ipsapirone prevents the ethanol-associated deficit of fetal rhombencephalic neurons by reducing apoptosis. The results of these studies strongly suggest that the ethanol-associated reduction in fetal rhombencephalic neurons that accompanies both in utero and in vitro exposure to physiological concentrations of ethanol is associated with increased apoptosis in these neurons. A physiological concentration of ethanol (i.e., 50 mM) increases apoptosis in fetal rhombencephalic neurons and decreases the number 5-HT neurons. It also appears that the 5-HT 1A agonist ipsapirone provides neuroprotection to these neurons by reducing apoptosis. Another mechanism by which ethanol-associated apoptosis can be blocked is by including serum proteins in the media at a concentration of 1% or higher; this concentration of serum proteins is high in comparison to the protein concentration in cerebrospinal fluid.