In utero exposure to serotonergic drugs alters neonatal expression of 5-HT1A receptor transcripts: a quantitative RT-PCR study

Abstract

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-HT1A 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-HT1 /5-HT2 agonist) from embryonic day E12-17 on expression of 5-HT1A receptor mRNA transcripts in brains of offspring at postnatal day 4 (PND 4). In offspring of both pCPA and 5-MT treated mothers, 5-HT1A 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-HT1A receptors (due to pCPA-induced 5-HT depletion) or over-stimulation (by the agonist 5-MT) during prenatal development significantly reduced expression of 5-HT1A receptor transcripts in neonatal offspring. This may occur by disruption of 5-HT1A gene transcription or by post-transcriptional mechanisms (such as altered translation or turnover of mRNA). Whatever the mechanism, reductions in 5-HT1A receptor transcripts following in utero exposure to serotonergic drugs could significantly impact the number of 5-HT1A receptors expressed in neonatal rat brain. Whether such effects will persist into adulthood remains to be determined.