title: Effects of L-methamphetamine treatment on cocaine- and food-maintained behavior in rhesus monkeys.
abstract: BACKGROUND
  Monoamine releasers with prominent dopaminergic actions, e.g., D-methamphetamine (D-MA), significantly reduce cocaine use and craving in clinical and preclinical laboratory studies. However, D-MA and related drugs also display high abuse potential, which limits their acceptability as agonist replacement medications for the management of Cocaine Use Disorder.
  
  
  OBJECTIVE
  The L-isomer of methamphetamine (L-MA), unlike D-MA, has preferential noradrenergic actions and is used medicinally with low, if any, abuse liability. The present study was conducted to determine whether L-MA could serve as an agonist replacement medication by both mimicking interoceptive effects of cocaine and decreasing intravenous (IV) cocaine self-administration.
  
  
  METHODS
  Separate groups (N = 4-5) of rhesus monkeys were studied to determine whether L-MA could (1) substitute for cocaine in subjects that discriminated intramuscular (IM) cocaine (0.4 mg/kg) from saline and (2) decrease IV cocaine self-administration under a second-order FR2(VR16:S) schedule of reinforcement.
  
  
  RESULTS
  L-MA, like D-MA but with approximately 5-fold lesser potency, substituted for cocaine in drug discrimination experiments in a dose-dependent manner. In IV self-administration studies, 5-10-day treatments with continuously infused L-MA (0.032-0.32 mg/kg/h, IV) dose-dependently decreased cocaine-maintained responding; the highest dosage reduced cocaine intake to levels of saline self-administration without appreciable effects on food-maintained responding.
  
  
  CONCLUSIONS
  These results indicate that L-MA both shares discriminative stimulus effects with cocaine and reduces cocaine self-administration in a behaviorally selective manner. L-MA and other compounds with a similar pharmacological profile deserve further evaluation for the management of Cocaine Use Disorder.
authors.affiliation: Department of Psychiatry, McLean Hospital-Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA. skohut@mclean.harvard.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kohut
authors.affiliation: Department of Psychiatry, McLean Hospital-Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Bergman
authors.affiliation: Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, Durham, NC, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Blough
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D002755:Choice Behavior / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D005260:Female; D005502:Food; D008253:Macaca mulatta; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology* / Q000627:therapeutic use; D012054:Reinforcement, Psychology; D012646:Self Administration; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D003042:Cocaine
keywords: Agonist therapy; Cocaine; Dopamine; Drug discrimination; Norepinephrine; Self-administration