title: Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats.
abstract: BACKGROUND
  Individuals with fetal alcohol spectrum disorder (FASD) are at increased risk for substance use disorders (SUD). In typically developing individuals, susceptibility to SUD is associated with alterations in dopamine and hypothalamic-pituitary-adrenal (HPA) systems, and their interactions. Prenatal alcohol exposure (PAE) alters dopamine and HPA systems, yet effects of PAE on dopamine-HPA interactions are unknown. Amphetamine-stress cross-sensitization paradigms were utilized to investigate sensitivity of dopamine and stress (HPA) systems, and their interactions following PAE.
  
  
  METHODS
  Adult Sprague-Dawley offspring from PAE, pair-fed, and ad libitum-fed control groups were assigned to amphetamine-(1-2 mg/kg) or saline-treated conditions, with injections every other day for 15 days. Fourteen days later, all animals received an amphetamine challenge (1 mg/kg) and 5 days later, hormones were measured under basal or acute stress conditions. Amphetamine sensitization (augmented locomotion, days 1-29) and cross-sensitization with acute restraint stress (increased stress hormones, day 34) were assessed.
  
  
  RESULTS
  PAE rats exhibited a lower threshold for amphetamine sensitization compared to controls, suggesting enhanced sensitivity of dopaminergic systems to stimulant-induced changes. Cross-sensitization between amphetamine (dopamine) and stress (HPA hormone) systems was evident in PAE, but not in control rats. PAE males exhibited increased dopamine receptor expression (medial prefrontal cortex (mPFC)) compared to controls.
  
  
  CONCLUSIONS
  PAE alters induction and expression of sensitization/cross-sensitization, as reflected in locomotor, neural, and endocrine changes, in a manner consistent with increased sensitivity of dopamine and stress systems. These results provide insight into possible mechanisms that could underlie increased prevalence of SUD, as well as the impact of widely prescribed stimulant medications among adolescents with FASD.
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada, kuban@chla.usc.edu.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Uban
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Comeau
authors.forename: Tamara
authors.initials: T
authors.lastname: Bodnar
authors.forename: Wayne K
authors.initials: WK
authors.lastname: Yu
authors.forename: Joanne
authors.initials: J
authors.lastname: Weinberg
authors.forename: Liisa A M
authors.initials: LA
authors.lastname: Galea
mesh_terms: D000208:Acute Disease; D000661:Amphetamine / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000523:psychology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology
chemical_list: D000697:Central Nervous System Stimulants; D011954:Receptors, Dopamine; D000661:Amphetamine; D004298:Dopamine