title: Amphetamine increases activity but not exploration in humans and mice.
abstract: BACKGROUND
  Cross-species quantification of physiological behavior enables a better understanding of the biological systems underlying neuropsychiatric diseases such as bipolar disorder (BD). Cardinal symptoms of manic BD include increased motor activity and goal-directed behavior, thought to be related to increased catecholamine activity, potentially selective to dopamine homeostatic dysregulation.
  
  
  OBJECTIVE
  The objective of this study was to test whether acute administration of amphetamine, a norepinephrine/dopamine transporter inhibitor and dopamine releaser, would replicate the profile of activity and exploration observed in both humans with manic BD and mouse models of mania.
  
  
  METHODS
  Healthy volunteers with no psychiatric history were randomized to a one-time dose of placebo (n = 25), 10 mg d-amphetamine (n = 18), or 20 mg amphetamine (n = 23). Eighty mice were administered one of four doses of d-amphetamine or vehicle. Humans and mice were tested in the behavioral pattern monitor (BPM), which quantifies motor activity, exploratory behavior, and spatial patterns of behavior.
  
  
  RESULTS
  In humans, the 20-mg dose of amphetamine increased motor activity as measured by acceleration without marked effects on exploration or spatial patterns of activity. In mice, amphetamine increased activity, decreased specific exploration, and caused straighter, one-dimensional movements in a dose-dependent manner.
  
  
  CONCLUSIONS
  Consistent with mice, amphetamine increased motoric activity in humans without increasing exploration. Given that BD patients exhibit heightened exploration, these data further emphasize the limitation of amphetamine-induced hyperactivity as a suitable model for BD. Further, these studies highlight the utility of cross-species physiological paradigms in validating biological mechanisms of psychiatric diseases.
authors.affiliation: Department of Psychiatry, University of California San Diego, 200 West Arbor Drive, La Jolla, Mailcode 8620, San Diego, CA, 92103-8620, USA. aminassian@ucsd.edu.|Center of Excellence for Stress and Mental Health (CESAMH), Veteran's Administration, San Diego, CA, USA. aminassian@ucsd.edu.
authors.forename: Arpi
authors.initials: A
authors.lastname: Minassian
authors.affiliation: Department of Psychiatry, University of California San Diego, 200 West Arbor Drive, La Jolla, Mailcode 8620, San Diego, CA, 92103-8620, USA.|VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Jared W
authors.initials: JW
authors.lastname: Young
authors.affiliation: Department of Psychiatry, University of California San Diego, 200 West Arbor Drive, La Jolla, Mailcode 8620, San Diego, CA, 92103-8620, USA.
authors.forename: Zackary A
authors.initials: ZA
authors.lastname: Cope
authors.affiliation: Department of Psychiatry, University of California San Diego, 200 West Arbor Drive, La Jolla, Mailcode 8620, San Diego, CA, 92103-8620, USA.
authors.forename: Brook L
authors.initials: BL
authors.lastname: Henry
authors.affiliation: Department of Psychiatry, University of California San Diego, 200 West Arbor Drive, La Jolla, Mailcode 8620, San Diego, CA, 92103-8620, USA.|VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Geyer
authors.affiliation: Department of Psychiatry, University of California San Diego, 200 West Arbor Drive, La Jolla, Mailcode 8620, San Diego, CA, 92103-8620, USA.
authors.forename: William
authors.initials: W
authors.lastname: Perry
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D001714:Bipolar Disorder / Q000523:psychology; D002395:Catecholamines / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D006040:Goals; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D013268:Stimulation, Chemical; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D002395:Catecholamines; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D003913:Dextroamphetamine; D004298:Dopamine
keywords: Amphetamine; Bipolar disorder; Catecholamines; Dopamine; Exploration; Mania; Motor activity