title: Beta-adrenoreceptor blockade abolishes atomoxetine-induced risk taking.
abstract: BACKGROUND
  Clinical studies have shown that patients with exaggerated risk-taking tendencies have high baseline levels of norepinephrine. In this work, we systemically manipulated norepinephrine levels in rats and studied their behavioral changes in a probabilistic discounting task, which is a paradigm for gauging risk taking.
  
  
  METHODS
  This study aims to explore the effects of the selective norepinephrine reuptake inhibitor (atomoxetine at doses of 0.6, 1.0 and 1.8 mg/kg), and receptor selective antagonists (propranolol at a single dose of 1.0/kg, and prazosin at a single dose of 0.1 mg/kg), on risk taking using a probabilistic discounting task. In this task, there were two levers available to rats: pressing the 'small/certain' lever guaranteed a single food pellet, and pressing the 'large/risky' lever yielded either four pellets or none. The probability of receiving four food pellets decreased across the four experimental blocks from 100% to 12.5%.
  
  
  RESULTS
  Atomoxetine increased the tendency to choose the large/risky lever. It significantly reduced the lose-shift effect (i.e. pressing a different lever after losing a trial), but did not affect the win-stay effect (i.e. pressing the same lever after winning a trial). Furthermore, co-administration of beta-adrenoreceptor antagonist, propranolol, eliminated the effects of atomoxetine on risk taking and the lose-shift effect; but co-administration of alpha1-adrenoreceptor antagonist, prazosin, did not.
  
  
  CONCLUSIONS
  Atomoxetine boosted NE levels and increased risk taking. This was because atomoxetine decreased rats' sensitivity to losses. These effects were likely mediated by beta-adrenoreceptor.
authors.affiliation: Beijing Key Laboratory of Learning and Cognition, Department of Psychology, Capital Normal University, Beijing 100048, China; Department of Psychology, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Fan Nils
authors.initials: FN
authors.lastname: Yang
authors.affiliation: Department of Psychology, Sun Yat-sen University, Guangzhou 510275, China. Electronic address: panj27@mail.sysu.edu.cn.
authors.forename: Jing Samantha
authors.initials: JS
authors.lastname: Pan
authors.affiliation: Beijing Key Laboratory of Learning and Cognition, Department of Psychology, Capital Normal University, Beijing 100048, China. Electronic address: lixw701@sina.cn.
authors.forename: Xinwang
authors.initials: X
authors.lastname: Li
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000069445:Atomoxetine Hydrochloride / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D012309:Risk-Taking
chemical_list: D000319:Adrenergic beta-Antagonists; D000069445:Atomoxetine Hydrochloride; D011433:Propranolol; D011224:Prazosin
keywords: Loss; Norepinephrinergic modulation; Probability discounting; Rat; Risk taking