title: Effects of prenatal immune activation and peri-adolescent  stress on amphetamine-induced conditioned place preference  in the rat.
abstract: BACKGROUND
  Addiction is a disease of learning and memory, as learning processes underlying acquisition, extinction, and reinstatement of drug-paired associations play central roles in addiction. Early developmental stress enhances risk for drug problems in adulthood. Environmental factors influencing learning and memory processes relevant to addiction remain incompletely characterized.
  
  
  OBJECTIVE
  To determine effects of prenatal immune activation and developmental stress on conditioned place preference to amphetamine, and reversal learning.
  
  
  METHODS
  Pregnant Sprague-Dawley rats were injected with polyinosinic:polycytidylic acid (poly I:C) or vehicle on gestational day 14. Half of the male offspring received 2 h of restraint stress at post-natal day 35. Behavioral testing was performed in adulthood.
  
  
  RESULTS
  Restraint stress inhibited acquisition of place preference to low-dose amphetamine (0.5 mg/kg), while poly I:C treatment had no measurable effect on place preference acquisition. In contrast, drug-induced reinstatement of preference for drug-paired chamber was enhanced in offspring of poly I:C-treated dams [F(1,25)05.31, p00.03]. Performance on a Morris water maze reversal learning task was impaired in poly I:C offspring. Reversal learning performance was correlated with place preference reinstatement in non-stressed (r200.42, p00.0095), but not stressed rats (r2 00.04, p00.49).
  
  
  CONCLUSIONS
  Prenatal immune activation enhances drug induced reinstatement of conditioned place preference. These data demonstrate longstanding impact on behaviors with potential influence on risk for drug relapse as a consequence of prenatal immune activation. Further study is needed to determine clinical and epidemiological consequences of similar exposures in human populations.
authors.affiliation: Psychiatry Service (V116A), Cincinnati Veterans Affairs Medical Center, 3200 Vine Street, Cincinnati, OH 45220, USA. neil.richtand@uc.edu
authors.forename: Neil M
authors.initials: NM
authors.lastname: Richtand
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ahlbrand
authors.forename: Paul S
authors.initials: PS
authors.lastname: Horn
authors.forename: Brad
authors.initials: B
authors.lastname: Chambers
authors.forename: Jon
authors.initials: J
authors.lastname: Davis
authors.forename: Stephen
authors.initials: S
authors.lastname: Benoit
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects*; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011070:Poly I-C / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012193:Reversal Learning / Q000187:drug effects; D013315:Stress, Psychological / Q000523:psychology
chemical_list: D000661:Amphetamine; D011070:Poly I-C