title: The effect of perinatal lead exposure on dopamine receptor D2 expression in morphine dependent rats.
abstract: The aim of this study was to investigate the behavioral and molecular effects of pre- and postnatal lead (Pb) exposure on the expression of morphine withdrawal and tolerance in adult rats. Rats were orally treated with 0.1% (1000ppm) lead acetate from conception, through gestation, up to postnatal day (PND) 28. Subsequently, behavioral experiments were conducted on adult (PND 60) male rats. To assess behavioral effects of morphine dependence in Pb-exposed rats two experimental models were used: naloxone-precipitated withdrawal signs and the assessment of morphine tolerance to antinociceptive effect in the tail-immersion test. Morphine withdrawal and tolerance were more expressed in Pb-exposed morphine administered rats than in morphine administered rats. In the case of morphine withdrawal signs the analysis of protein (Western blotting) and mRNA (RT PCR) expression revealed significantly higher dopamine D2 receptor (D2R) expression in prefrontal cortex, but not in striatum and hippocampus, in Pb-exposed morphine administered rats than in morphine administered rats. Differently, in the case of morphine tolerance the significant upregulation of D2R protein and mRNA expression in hippocampus, but not in prefrontal cortex or striatum, was demonstrated in Pb-exposed and morphine administered rats in comparison with morphine administered. These findings suggest that in morphine withdrawal and tolerant rats the perinatal Pb-exposure can affect D2R expression in brain region-specific manner. Immunohistochemical assessment of D2R expression in hippocampus showed translocation of D2R from membrane-cytoplasm in control rats to nucleus in morphine administered rats. Perinatal Pb-exposure did not induce the changes in the localization of D2R irrespective of morphine effect.
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093 Lublin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Listos
authors.forename: Irena
authors.initials: I
authors.lastname: Baranowska-Bosiacka
authors.forename: Sylwia
authors.initials: S
authors.lastname: Talarek
authors.forename: Piotr
authors.initials: P
authors.lastname: Listos
authors.forename: Jolanta
authors.initials: J
authors.lastname: Orzelska
authors.forename: Sylwia
authors.initials: S
authors.lastname: Fidecka
authors.forename: Izabela
authors.initials: I
authors.lastname: Gutowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kolasa
authors.forename: Marta
authors.initials: M
authors.lastname: Rybicka
authors.forename: Dariusz
authors.initials: D
authors.lastname: Chlubek
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007150:Immunohistochemistry; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects; D009021:Morphine Dependence / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis* / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004785:Environmental Pollutants; D017448:Receptors, Dopamine D2; D007854:Lead; D009020:Morphine
keywords: Dependence; Dopamine D2 receptor expression; Lead (Pb); Morphine tolerance; Morphine withdrawal signs