title: Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: correlations between behavior and neurochemistry.
abstract: BACKGROUND
  Considerable evidence indicates that amphetamine derivatives can deplete brain monoaminergic neurotransmitters. However, the behavioral and cognitive consequences of neurochemical depletions induced by amphetamines are not well established.
  
  
  OBJECTIVE
  In this study, mice were exposed to dosing regimens of 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH), or parachloroamphetamine (PCA) known to deplete the monoamine neurotransmitters dopamine and serotonin, and the effects of these dosing regimens on learning and memory were assessed.
  
  
  METHODS
  In the same animals, we determined deficits in learning and memory via passive avoidance (PA) behavior and changes in tissue content of monoamine neurotransmitters and their primary metabolites in the striatum, frontal cortex, cingulate, hippocampus, and amygdala via ex vivo high-pressure liquid chromatography.
  
  
  RESULTS
  Exposure to METH and PCA impaired PA performance and resulted in significant depletions of dopamine, serotonin, and their metabolites in several brain regions. Multiple linear regression analysis revealed that the tissue concentration of dopamine in the anterior striatum was the strongest predictor of PA performance, with an additional significant contribution by the tissue concentration of the serotonin metabolite 5-hydroxyindoleacetic acid in the cingulate. In contrast to the effects of METH and PCA, exposure to MDMA did not deplete anterior striatal dopamine levels or cingulate levels of 5-hydroxyindoleacetic acid, and it did not impair PA performance.
  
  
  CONCLUSIONS
  These studies demonstrate that certain amphetamines impair PA performance in mice and that these impairments may be attributable to specific neurochemical depletions.
authors: Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Yerkes Imaging Center, 954 Gatewood Road, Atlanta, GA 30322-4250, USA. acmurna@emory.edu
authors: Kevin Sean
authors: KS
authors: Murnane
authors: Shane Alan
authors: SA
authors: Perrine
authors: Brendan James
authors: BJ
authors: Finton
authors: Matthew Peter
authors: MP
authors: Galloway
authors: Leonard Lee
authors: LL
authors: Howell
authors: William Edward
authors: WE
authors: Fantegrossi
mesh_terms: D018663:Adrenergic Agents / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016014:Linear Models; D008297:Male; D008568:Memory / Q000187:drug effects; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000008:administration & dosage / Q000633:toxicity; D010133:p-Chloroamphetamine / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D018663:Adrenergic Agents; D018490:Serotonin Agents; D012701:Serotonin; D008694:Methamphetamine; D010133:p-Chloroamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine