title: Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats.
abstract: BACKGROUND
  d-Methamphetamine (METH) addiction is a serious public health concern for which successful treatment remains elusive. Immunopharmacotherapy has been shown to attenuate locomotor and thermoregulatory effects of METH. The current study investigated whether active vaccination against METH could alter intravenous METH self-administration in rats.
  
  
  METHODS
  Male Sprague-Dawley rats (Experiment 1: N=24; Experiment 2: N=18) were vaccinated with either a control keyhole-limpet hemocyanin conjugate vaccine (KLH) or a candidate anti-METH vaccine (MH6-KLH) or. Effects of vaccination on the acquisition of METH self-administration under two dose conditions (0.05, 0.1mg/kg/inf) and post-acquisition dose-substitution (0, 0.01, 0.05, 0.20mg/kg/inf, Experiment 1; 0.01, 0.05, 0.10, 0.15mg/kg/inf, Experiment 2) during steady-state responding were investigated. Plasma METH concentrations were determined 30min after an acute challenge dose of 3.2mg/kg METH.
  
  
  RESULTS
  Active vaccination inhibited the acquisition of METH self-administration under the 0.1mg/kg/inf dose condition, with 66% of the MH6-KLH-vaccinated rats compared to 100% of the controls reaching criteria, and produced transient and dose-dependent effects on self-administration during the maintenance phase. Under the 0.05mg/kg/inf dose condition, MH6-KLH-vaccinated rats initially self-administered more METH than controls, but then self-administration decreased across the acquisition phase relative to controls; a subsequent dose-response assessment confirmed that MH6-KLH-vaccinated rats failed to acquire METH self-administration. Finally, plasma METH concentrations were higher in MH6-KLH-vaccinated rats compared to controls after an acute METH challenge, and these were positively correlated with antibody titers.
  
  
  CONCLUSIONS
  These data demonstrate that active immunopharmacotherapy for METH attenuates the acquisition of METH self-administration.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Miller
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Aarde
authors.affiliation: Departments of Chemistry, Immunology and Microbial Science, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: A Y
authors.initials: AY
authors.lastname: Moreno
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Creehan
authors.affiliation: Departments of Chemistry, Immunology and Microbial Science, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Janda
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: mtaffe@scripps.edu.
authors.forename: M A
authors.initials: MA
authors.lastname: Taffe
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D006433:Hemocyanins / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000008:administration & dosage
chemical_list: D014612:Vaccines; D008694:Methamphetamine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin
keywords: Active vaccination; Drug addiction; Immunopharmacotherapy; Methamphetamine; Self-administration