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In utero exposure to serotonergic drugs alters neonatal expression of 5‐HT 1A receptor transcripts: a quantitative RT‐PCR study
Author(s) -
Lauder Jean M.,
Liu Jiangping,
Grayson Dennis R.
Publication year - 2000
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(99)00085-4
Subject(s) - serotonergic , offspring , receptor , endocrinology , serotonin , medicine , biology , 5 ht receptor , agonist , in utero , gene expression , stimulation , fetus , gene , pregnancy , genetics
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 ( p CPA; 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 p CPA and 5‐MT treated mothers, 5‐HT 1A transcripts were significantly reduced compared to vehicle controls, although effects of p CPA were greater than those of 5‐MT. These results indicate that either under‐stimulation of 5‐HT 1A receptors (due to p CPA‐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.