A persistent deficit of serotonin neurons in the offspring of ethanol-fed dams: protective effects of maternal ipsapirone treatment.
An earlier study from this laboratory found a significant reduction in the density of serotonin (5-HT) neurons in the dorsal and median raphe and in the B9 complex of postnatal day 5 (PN5) offspring of female rats that consumed ethanol on a chronic basis prior to parturition. In addition, we demonstrated that maternal treatment with the 5-HT(1A) agonist ipsapirone (3 mg/kg) prevented the ethanol-associated reduction in 5-HT neurons. The present investigation examined whether there was a persistent deficit of 5-HT-immunopositive neurons in the dorsal and median raphe of the offspring of ethanol-fed dams. We also evaluated whether a lower ipsapirone dose (1 mg/kg) was protective to developing 5-HT neurons in the offspring of ethanol-fed dams. The offspring of ethanol-fed dams exhibited an apparent lasting reduction in the density of 5-HT neurons in the dorsal and median raphe. The density of 5-HT neurons in control offspring was comparable at PN5 and PN19, but at both ages the offspring of ethanol-fed dams had a significant deficit of 5-HT neurons in the dorsal and median raphe. The lack of recovery in the density of 5-HT-immunopositive neurons in the offspring of ethanol-fed dams between PN5 and PN19 suggests and that the reduction was long lasting. The protective effects of ipsapirone appeared to be dose dependent. The density of 5-HT neurons in the dorsal and median raphe of PN5 (prior study) and PN19 offspring of ethanol-fed dams that were treated with 3 mg/kg of ipsapirone between gestational day 13 (G13) and G20 was comparable to that of control offspring. However, the effects of maternal treatment of ethanol-fed dams with the 1 mg/kg dose were variable, and some abnormalities were detected in the offspring of ipsapirone-treated control dams.
Tajuddin
N F
NF
Division of Molecular and Cellular Biochemistry, Department of Cell Biology, Neurobiology, and Anatomy, Loyola University, Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA.
Druse
M J
MJ
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002452:Cell Count; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D011743:Pyrimidines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D018696:Neuroprotective Agents; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000431:Ethanol; C043077:ipsapirone