In utero exposure to serotonergic drugs alters neonatal expression of 5-HT(1A) receptor transcripts: a quantitative RT-PCR study.
In embryonic rat brain, serotonin (5-HT) acts as a differentiation signal for 5-HT neurons and their target cells during midgestation. Serotonin receptors expressed during this period include the 5-HT(1A) subtype, which may mediate some of these developmental effects. Using the highly sensitive method of competitive RT-PCR, we quantified the effects of maternal treatment with either p-chlorophenylalanine (pCPA; which depletes 5-HT in embryonic rat brain) or 5-methoxytryptamine (5-MT; a general 5-HT(1) /5-HT(2) agonist) from embryonic day E12-17 on expression of 5-HT(1A) receptor mRNA transcripts in brains of offspring at postnatal day 4 (PND 4). In offspring of both pCPA and 5-MT treated mothers, 5-HT(1A) transcripts were significantly reduced compared to vehicle controls, although effects of pCPA were greater than those of 5-MT. These results indicate that either under-stimulation of 5-HT(1A) receptors (due to pCPA-induced 5-HT depletion) or over-stimulation (by the agonist 5-MT) during prenatal development significantly reduced expression of 5-HT(1A) receptor transcripts in neonatal offspring. This may occur by disruption of 5-HT(1A) gene transcription or by post-transcriptional mechanisms (such as altered translation or turnover of mRNA). Whatever the mechanism, reductions in 5-HT(1A) receptor transcripts following in utero exposure to serotonergic drugs could significantly impact the number of 5-HT(1A) receptors expressed in neonatal rat brain. Whether such effects will persist into adulthood remains to be determined.
Lauder
J M
JM
Department of Cell Biology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7090, USA.
Liu
J
J
Grayson
D R
DR
D008735:5-Methoxytryptamine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000196:embryology / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D005260:Female; D010134:Fenclonine / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000235:genetics*; D044263:Receptors, Serotonin, 5-HT1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D008735:5-Methoxytryptamine; D010134:Fenclonine