The alterations in CNS serotonergic mechanisms caused by neonatal chlorpyrifos exposure are permanent.
Fetal or neonatal exposure to chlorpyrifos (CPF) or related organophosphate pesticides leads to abnormalities of brain cell development, synaptic function, and behavior. Recent studies in rats indicate profound effects on serotonin (5HT) systems that originate during CPF exposure and that are still present at 2 months posttreatment in the young adult. To determine if these changes are permanent, we administered 1 mg/kg of CPF daily to neonatal rats on postnatal days 1-4, a regimen devoid of systemic toxicity, and examined 5HT synaptic markers at 5 months of age: radioligand binding to 5HT1A and 5HT2 receptors and to the 5HT transporter. There were global elevations in all three synaptic proteins, with pronounced sex selectivity (effects on males>females) and a regional hierarchy of effects, viz. striatum>midbrain approximately brainstem>cerebral cortex. Because there is a normal sex disparity for 5HT synaptic proteins, with females having higher values than males, the increase caused by CPF exposure in males completely eliminated this difference. Our findings at 5 months of age replicate those seen in young adulthood and strongly suggest that the effects of neonatal CPF exposure on 5HT systems are permanent.
Slotkin
Theodore A
TA
Department of Pharmacology and Cancer Biology, Box 3813 DUMC, Duke University Medical Center, Durham, NC 27710, USA. t.slotkin@duke.edu
Seidler
Frederic J
FJ
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004390:Chlorpyrifos / Q000633:toxicity*; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D012737:Sex Factors
D007306:Insecticides; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D044302:Receptor, Serotonin, 5-HT1B; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D004390:Chlorpyrifos