Effects of acute and chronic prenatal nicotine treatment on central catecholamine systems of male and female rat fetuses and offspring.
The effect of acute and chronic prenatal administration of nicotine on central catecholamine systems was studied in Long Evans rats. A single injection of nicotine (1 mg/kg s.c.) to urethane-anesthetized time-pregnant dams at gestational day (GD) 21 increased dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid (determined by radioenzymatic assay and high-performance liquid chromatography with electrochemical detection, respectively) in male and female fetal forebrain within 30 min. No significant change was seen in norepinephrine (NE) and MOPEG, but the MOPEG/NE ratio increased in male fetuses. After the administration of nicotine by an osmotic minipump (0.25 mg/kg x hour or vehicle for controls) between GD 12 and 18/19, MOPEG was elevated at GD 18 and reduced at postnatal day (PN) 15 in both sexes; the reduction persisted in males until adulthood (2.5 months). 3,4-dihydroxyphenylacetic acid was affected by chronic drug treatment only in males with an increase at GD 18 and PN 15 and a decrease in adulthood. In contrast, homovanillic acid was reduced in adult offspring of both sexes. Male NE and dopamine of both sexes was above control level at PN 15. Cross-fostering data demonstrate that the changes were due to prenatal influences. The observations indicate that central fetal catecholamine systems are responsive to acute administration of nicotine and that chronic prenatal exposure to the drug results in persistent alterations in the functional state of these neurons. The drug-induced pattern of neurochemical alterations changes during ontogeny until adulthood; it depends upon the sex of the offspring.
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Institute of Pharmacology, University of Zürich, Switzerland.
Lichtensteiger
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006719:Homovanillic Acid / Q000032:analysis; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D012737:Sex Factors
D002395:Catecholamines; D015102:3,4-Dihydroxyphenylacetic Acid; D009538:Nicotine; D006719:Homovanillic Acid