title: Sex-Dependent Changes in Striatal Dopamine Transport in Preadolescent Rats Exposed Prenatally and/or Postnatally to Methamphetamine.
abstract: Methamphetamine (MA) is the most commonly used psychostimulant drug, the chronic abuse of which leads to neurodegenerative changes in the brain. The global use of MA is increasing, including in pregnant women. Since MA can cross both placental and haematoencephalic barriers and is also present in maternal milk, children of chronically abused mothers are exposed prenatally as well as postnatally. Women seem to be more vulnerable to some aspects of MA abuse than men. MA is thought to exert its effects among others via direct interactions with dopamine transporters (DATs) in the brain tissue. Sexual dimorphism of the DAT system could be a base of sex-dependent actions of MA observed in behavioural and neurochemical studies. Possible sex differences in the DATs of preadolescent offspring exposed to MA prenatally and/or postnatally have not yet been evaluated. We examined the striatal synaptosomal DATs (the activity and density of surface expressed DATs and total DAT expression) in preadolescent male and female Wistar rats (31-35-day old animals) exposed prenatally and/or postnatally to MA (daily 5 mg/kg, s.c. to mothers during pregnancy and lactation). To distinguish between specific and nonspecific effects of MA on DATs, we also evaluated the in vitro effects of lipophilic MA on the fluidity of striatal membranes isolated from preadolescent and young adult rats of both sexes. We observed similar changes in the DATs of preadolescent rats exposed prenatally or postnatally (MA-mediated drop in the reserve pool but no alterations in surface-expressed DATs). However, prenatal exposure evoked significant changes in males and postnatal exposure in females. A significant decrease in the activity of surface-expressed DATs was found only in postnatally exposed females sensitized to MA via prenatal exposure. MA applied in vitro increased the fluidity of striatal membranes of preadolescent female but not male rats. In summary, DATs of preadolescent males are more sensitive to prenatal MA exposure via changes in the reserve pool and those of preadolescent females to postnatal MA exposure via the same mechanism. The combination of prenatal and postnatal MA exposure increases the risk of dopaminergic deficits via alterations in the activity of surface-expressed DATs especially in preadolescent females. MA-mediated changes in DATs of preadolescent females could be still enhanced via nonspecific disordering actions of MA on striatal membranes.
authors.affiliation: National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic.|Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Sirova
authors.affiliation: National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic. zdenka.kristofikova@nudz.cz.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Kristofikova
authors.affiliation: National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Vrajova
authors.affiliation: National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Fujakova-Lipski
authors.affiliation: National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ripova
authors.affiliation: Institute of Computer Science, The Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Klaschka
authors.affiliation: Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Romana
authors.initials: R
authors.lastname: Slamberova
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008694:Methamphetamine; D004298:Dopamine
keywords: Dopamine transporter; Membrane fluidity; Methamphetamine; Sex differences