A vaccine against methamphetamine attenuates its behavioral effects in mice

Drug Alcohol Depend. 2013 Apr 1;129(1-2):41-8. doi: 10.1016/j.drugalcdep.2012.09.007. Epub 2012 Sep 28.


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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amphetamine-Related Disorders / immunology*
  • Amphetamine-Related Disorders / prevention & control*
  • Amphetamine-Related Disorders / psychology
  • Animals
  • Antibodies / analysis
  • Behavior, Animal / physiology*
  • Carrier Proteins / immunology
  • Central Nervous System Stimulants / chemistry
  • Central Nervous System Stimulants / immunology*
  • Central Nervous System Stimulants / pharmacology
  • Conditioning, Operant / physiology
  • Data Interpretation, Statistical
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hemocyanins / immunology
  • Immunization / methods
  • Methamphetamine / chemistry
  • Methamphetamine / immunology*
  • Methamphetamine / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Motor Activity / physiology
  • Reward
  • Vaccines / therapeutic use*


  • Antibodies
  • Carrier Proteins
  • Central Nervous System Stimulants
  • Vaccines
  • Methamphetamine
  • Hemocyanins
  • keyhole-limpet hemocyanin