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Prenatal immune challenge in rats: effects of polyinosinic-polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine.
Neurotoxicol Teratol. 2015 Jan-Feb; 47:54-65.NT

Abstract

Prenatal maternal immune activation increases risk for schizophrenia and/or autism. Previous data suggest that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats influences the severity of effect in the offspring as does the exposure period. We treated gravid Sprague-Dawley rats from E14 to 18 with 8mg/kg/day Poly IC or saline. The Poly IC group was divided into those that gained the least weight or lost (Poly IC (L)) and those that gained the most (Poly IC (H)) weight. There were no effects of Poly IC on anxiety (elevated zero-maze, open-field, object burying), or Morris water maze cued learning or working memory or Cincinnati water maze egocentric learning. The Poly IC (H) group males had decreased acoustic startle whereas Poly IC (L) females had reduced startle and increased PPI. Poly IC offspring showed exaggerated hyperactivity in response to amphetamine (primarily in the Poly IC (H) group) and attenuated hyperactivity in response to MK-801 challenge (primarily in the Poly IC (L) group). Poly IC (L) males showed reduced cued conditioned freezing; both sexes showed less time in the dark in a light-dark test, and the Poly IC groups showed impaired Morris water maze hidden platform acquisition and probe performance. The data demonstrate that offspring from the most affected dams were more affected than those from less reactive dams indicating that degree of maternal immune activation predicts severity of effects on offspring behavior.

Authors+Show Affiliations

Division of Child Neurology, Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229, United States; Department of Pediatrics, College of Medicine, University of Cincinnati, United States. Electronic address: charles.vorhees@cchmc.org.Department of Pharmacology and Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, United States.Division of Child Neurology, Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229, United States; Department of Pediatrics, College of Medicine, University of Cincinnati, United States.Division of Child Neurology, Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229, United States; Department of Pediatrics, College of Medicine, University of Cincinnati, United States.Division of Child Neurology, Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229, United States; Department of Pediatrics, College of Medicine, University of Cincinnati, United States.Psychiatry Service, V-116A, VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA 92161, United States.Division of Child Neurology, Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229, United States; Department of Pediatrics, College of Medicine, University of Cincinnati, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

25450663

Citation

Vorhees, Charles V., et al. "Prenatal Immune Challenge in Rats: Effects of Polyinosinic-polycytidylic Acid On Spatial Learning, Prepulse Inhibition, Conditioned Fear, and Responses to MK-801 and Amphetamine." Neurotoxicology and Teratology, vol. 47, 2015, pp. 54-65.
Vorhees CV, Graham DL, Braun AA, et al. Prenatal immune challenge in rats: effects of polyinosinic-polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine. Neurotoxicol Teratol. 2015;47:54-65.
Vorhees, C. V., Graham, D. L., Braun, A. A., Schaefer, T. L., Skelton, M. R., Richtand, N. M., & Williams, M. T. (2015). Prenatal immune challenge in rats: effects of polyinosinic-polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine. Neurotoxicology and Teratology, 47, 54-65. https://doi.org/10.1016/j.ntt.2014.10.007
Vorhees CV, et al. Prenatal Immune Challenge in Rats: Effects of Polyinosinic-polycytidylic Acid On Spatial Learning, Prepulse Inhibition, Conditioned Fear, and Responses to MK-801 and Amphetamine. Neurotoxicol Teratol. 2015 Jan-Feb;47:54-65. PubMed PMID: 25450663.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prenatal immune challenge in rats: effects of polyinosinic-polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine. AU - Vorhees,Charles V, AU - Graham,Devon L, AU - Braun,Amanda A, AU - Schaefer,Tori L, AU - Skelton,Matthew R, AU - Richtand,Neil M, AU - Williams,Michael T, Y1 - 2014/11/08/ PY - 2014/07/12/received PY - 2014/10/23/revised PY - 2014/10/31/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/9/12/medline KW - (+)-Amphetamine-induced locomotor activity KW - MK-801-induced locomotor activity KW - Morris water maze KW - Polyinosinic–polycytidylic acid KW - Prenatal immune activation KW - Rat SP - 54 EP - 65 JF - Neurotoxicology and teratology JO - Neurotoxicol Teratol VL - 47 N2 - Prenatal maternal immune activation increases risk for schizophrenia and/or autism. Previous data suggest that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats influences the severity of effect in the offspring as does the exposure period. We treated gravid Sprague-Dawley rats from E14 to 18 with 8mg/kg/day Poly IC or saline. The Poly IC group was divided into those that gained the least weight or lost (Poly IC (L)) and those that gained the most (Poly IC (H)) weight. There were no effects of Poly IC on anxiety (elevated zero-maze, open-field, object burying), or Morris water maze cued learning or working memory or Cincinnati water maze egocentric learning. The Poly IC (H) group males had decreased acoustic startle whereas Poly IC (L) females had reduced startle and increased PPI. Poly IC offspring showed exaggerated hyperactivity in response to amphetamine (primarily in the Poly IC (H) group) and attenuated hyperactivity in response to MK-801 challenge (primarily in the Poly IC (L) group). Poly IC (L) males showed reduced cued conditioned freezing; both sexes showed less time in the dark in a light-dark test, and the Poly IC groups showed impaired Morris water maze hidden platform acquisition and probe performance. The data demonstrate that offspring from the most affected dams were more affected than those from less reactive dams indicating that degree of maternal immune activation predicts severity of effects on offspring behavior. SN - 1872-9738 UR - https://www.unboundmedicine.com/medline/citation/25450663/Prenatal_immune_challenge_in_rats:_effects_of_polyinosinic_polycytidylic_acid_on_spatial_learning_prepulse_inhibition_conditioned_fear_and_responses_to_MK_801_and_amphetamine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0892-0362(14)00179-2 DB - PRIME DP - Unbound Medicine ER -