title: A vaccine against methamphetamine attenuates its behavioral effects in mice.
abstract: BACKGROUND
  Vaccines have treatment potential for methamphetamine (MA) addiction. We tested whether a conjugate vaccine against MA (succinyl-methamphetamine-keyhole limpet hemocyanin carrier protein; SMA-KLH) would generate MA antibodies and alter MA-induced behaviors.
  
  
  METHODS
  Mice were injected with SMA-KLH and received booster administrations 3 and 20 weeks later. Serum antibody titers reached peak levels by 4-6 weeks, remained at a modest level through 18 weeks, peaked again at 22 weeks after the second boost, and were still elevated at 35 weeks. At 7 weeks, groups of vaccinated and non-vaccinated mice were administered one of three MA doses (1, 2 or 3 mg/kg) to assess locomotor activity.
  
  
  RESULTS
  Non-vaccinated mice showed dose-dependent effects of MA with hypolocomotion at the lowest dose and elevated activity levels at the highest dose. Both dose effects were reduced in SMA-KLH groups, particularly low dose-induced hypolocomotion at later times post MA administration. Separate groups of vaccinated and non-vaccinated mice were trained in MA place conditioning at 30 weeks with either 0 (vehicle) or 0.5mg/kg MA. Although times spent in the MA-paired side did not differ between groups on test vs. baseline sessions, SMA-KLH mice conditioned with MA showed reduced conditioned approach behaviors and decreased conditioned activity levels compared to control groups.
  
  
  CONCLUSIONS
  These data suggest SMA-KLH attenuates the ability of MA to support place conditioning and reduces or delays its locomotor effects. Overall, results support SMA-KLH as a candidate MA vaccine.
authors.affiliation: Immunology Allergy & Rheumatology, Department of Medicine, The Michael E Debakey Veteran's Medical Affairs Center, Houston, TX 77030, United States.
authors.forename: Xiaoyun Y
authors.initials: XY
authors.lastname: Shen
authors.forename: Therese A
authors.initials: TA
authors.lastname: Kosten
authors.forename: Angel Y
authors.initials: AY
authors.lastname: Lopez
authors.forename: Berma M
authors.initials: BM
authors.lastname: Kinsey
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
authors.forename: Frank M
authors.initials: FM
authors.lastname: Orson
mesh_terms: D019969:Amphetamine-Related Disorders / Q000276:immunology* / Q000517:prevention & control* / Q000523:psychology; D000818:Animals; D000906:Antibodies / Q000032:analysis; D001522:Behavior, Animal / Q000502:physiology*; D002352:Carrier Proteins / Q000276:immunology; D000697:Central Nervous System Stimulants / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D003216:Conditioning, Operant / Q000502:physiology; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007114:Immunization / Q000379:methods; D008694:Methamphetamine / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000502:physiology; D012201:Reward; D014612:Vaccines / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D014612:Vaccines; D008694:Methamphetamine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin