Preadolescent Phthalate (DEHP) Exposure Is Associated With Elevated Locomotor Activity and Reward-Related Behavior and a Reduced Number of Tyrosine Hydroxylase Positive Neurons in Post-Adolescent Male and Female Rats

被引:24
作者
Holahan, Matthew R. [1 ]
Smith, Catherine A. [1 ]
Luu, Bryan E. [2 ,3 ]
Storey, Kenneth B. [2 ,3 ]
机构
[1] Carleton Univ, Dept Neurosci, Ottawa, ON K1S 5B6, Canada
[2] Carleton Univ, Inst Biochem, Ottawa, ON K1S 5B6, Canada
[3] Carleton Univ, Dept Biol, Ottawa, ON K1S 5B6, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
juvenile; adolescence; reward; dopamine; ventral tegmental area; substantia nigra; NUCLEUS-ACCUMBENS SHELL; ACUTE POSTNATAL EXPOSURE; MIDBRAIN DOPAMINERGIC-NEURONS; TRANSCRIPTION FACTOR PITX3; DI(2-ETHYLHEXYL)PHTHALATE DEHP; DI-(2-ETHYLHEXYL) PHTHALATE; PROGRESSIVE RATIO; REPRODUCTIVE DEVELOPMENT; ELECTRICAL-ACTIVITY; PARKINSONS-DISEASE;
D O I
10.1093/toxsci/kfy171
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Phthalate administration to male rats has been shown to negatively impact neural development while development of the female rat brain is less affected. Because a number of exogenous agents have been shown to interfere with dopamine function, we evaluated post-adolescent behavioral (operant conditioning for food reward and locomotor activity), histological (tyrosine hydroxylase; TH), and genetic (mRNA levels) outcomes of preadolescent (postnatal days [PND] 16-22) phthalate exposure. Male and female Long-Evans rats were administered 4 doses (0,1,10, or 20 mg/kg) of di-(2-ethylhexyl)phthalate (DEHP) i.p. from PND16 to 22. Rats were trained on an operant task to bar press for chocolate-flavored pellets from PND55-63 then euthanized on PND78. The 10 mg/kg DEHP dose was associated with elevated bar pressing for food reward during acquisition and extinction while the 20 mg/kg dose was associated with elevated locomotor activity in both males and females. Stereological analysis revealed reduced TH+ densities in the SNc in DEHP- (10 and 20 mg/kg) treated male and female rats. In the VTA, TH+ staining was reduced in male rats treated with 10 or 20 mg/kg DEHP while in females, the TH: CV ratio was higher at the 10 mg/kg dose compared with controls. An examination of Th mRNA showed a main effect of sex with females showing increased Th expression at all DEHP doses. The present results show that preadolescent phthalate exposure results in detrimental dopaminergic system development impacting neurobehavioral function in post-adolescent rats.
引用
收藏
页码:512 / 530
页数:19
相关论文
共 105 条
[1]   Optogenetic Interrogation of Dopaminergic Modulation of the Multiple Phases of Reward-Seeking Behavior [J].
Adamantidis, Antoine R. ;
Tsai, Hsing-Chen ;
Boutrel, Benjamin ;
Zhang, Feng ;
Stuber, Garret D. ;
Budygin, Evgeny A. ;
Tourino, Clara ;
Bonci, Antonello ;
Deisseroth, Karl ;
de Lecea, Luis .
JOURNAL OF NEUROSCIENCE, 2011, 31 (30) :10829-10835
[2]   N-methyl-D-aspartate and dopamine receptor involvement in the modulation of locomotor activity and memory processes [J].
Adriani, W ;
Felici, A ;
Sargolini, F ;
Roullet, P ;
Usiello, A ;
Oliverio, A ;
Mele, A .
EXPERIMENTAL BRAIN RESEARCH, 1998, 123 (1-2) :52-59
[3]   Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances [J].
Akingbemi, BT ;
Ge, RS ;
Klinefelter, GR ;
Zirkin, BR ;
Hardy, MP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (03) :775-780
[4]   Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate [J].
Akingbemi, BT ;
Youker, RT ;
Sottas, CM ;
Ge, RS ;
Katz, E ;
Klinefelter, GR ;
Zirkin, BR ;
Hardy, MP .
BIOLOGY OF REPRODUCTION, 2001, 65 (04) :1252-1259
[5]   Do children really recover better? Neurobehavioural plasticity after early brain insult [J].
Anderson, Vicki ;
Spencer-Smith, Megan ;
Wood, Amanda .
BRAIN, 2011, 134 :2197-2221
[6]   Differential effects of clozapine, metoclopramide, haloperidol and risperidone on acquisition and performance of operant responding in rats [J].
Baker, Tyson W. ;
Florczynski, Matthew M. ;
Beninger, Richard J. .
PSYCHOPHARMACOLOGY, 2015, 232 (09) :1535-1543
[7]   DISSOCIATING THE EFFECTS OF ALTERED DOPAMINERGIC FUNCTION ON PERFORMANCE AND LEARNING [J].
BENINGER, RJ .
BRAIN RESEARCH BULLETIN, 1989, 23 (4-5) :365-371
[8]   Determination of the Di-(2-Ethylhexyl) Phthalate NOAEL for Reproductive Development in the Rat: Importance of the Retention of Extra Animals to Adulthood [J].
Blystone, Chad R. ;
Kissling, Grace E. ;
Bishop, Jack B. ;
Chapin, Robert E. ;
Wolfe, Gary W. ;
Foster, Paul M. D. .
TOXICOLOGICAL SCIENCES, 2010, 116 (02) :640-646
[9]   Use of frozen sections to determine neuronal number in the murine hippocampus and neocortex using the optical disector and optical fractionator [J].
Bonthius, DJ ;
McKim, R ;
Koele, L ;
Harb, H ;
Karacay, B ;
Mahoney, J ;
Pantazis, NJ .
BRAIN RESEARCH PROTOCOLS, 2004, 14 (01) :45-57
[10]   Reproductive Effects of Di(2-ethylhexyl)phthalate in Immature Male Rats and Its Relation to Cholesterol, Testosterone, and Thyroxin Levels [J].
Botelho, Giuliana G. K. ;
Golin, Munisa ;
Bufalo, Aedra C. ;
Morais, Rosana N. ;
Dalsenter, Paulo R. ;
Martino-Andrade, Anderson J. .
ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, 2009, 57 (04) :777-784