Prenatal haloperidol exposure: effects on brain weights and caudate neurotransmitter levels in rats.
Monoamines may exert a trophic effect on early brain development. To assess the role of dopamine in prenatal neurological development of the rat, haloperidol (HAL) was given in daily 2.5 or 5 mg/kg SC doses to dams over gestational days 6 to 20. This treatment regime did not enhance fetal mortality, but did produce reliable, if modest, stunting of the body and brain weight of offspring. The 5 mg/kg HAL dose consistently reduced offspring brain weight to roughly 90% of controls. This effect was probably permanent, in that it was seen throughout maturation and in adults as late as 140 days of postnatal age. Appropriate controls showed that this effect was not due to drug-induced reductions in food intake, to the presence of HAL in maternal milk, or to behavioral abnormalities in HAL-exposed dams. These effects had, at best, modest regional specificity, in that most brain regions were affected, independently of degree of dopaminergic innervation. Closer investigation of HAL effects on the striatum suggested that this permanent weight reduction was not accompanied by alterations in striatal concentrations of monoamines, monoamine metabolites, amino acids, choline, acetylcholine, DNA, protein, or water. It is concluded that prenatal HAL does stunt growth, but that this effect may not involve a direct drug influence restricted to the fetal dopamine system in the brain.
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
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Williams
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Ali
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Scalzo
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Soliman
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Holson
D000109:Acetylcholine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D004247:DNA; D006220:Haloperidol; D000109:Acetylcholine