Altered methamphetamine place conditioning in mice vaccinated with a succinyl-methamphetamine-tetanus-toxoid vaccine.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 9208821 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-0391 (Electronic) Linking ISSN: 10550496 NLM ISO Abbreviation: Am J Addict Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Wiley-Blackwell
      Original Publication: Washington, DC : American Psychiatric Press, c1992-
    • Subject Terms:
      Vaccination*; Amphetamine-Related Disorders/*prevention & control ; Conditioning, Psychological/*drug effects ; Methamphetamine/*immunology ; Methamphetamine/*pharmacology ; Tetanus Toxoid/*immunology; Adjuvants, Immunologic ; Aluminum Hydroxide/administration & dosage ; Animals ; Antibodies/blood ; Avoidance Learning/drug effects ; Brain/drug effects ; Brain/metabolism ; Female ; Methamphetamine/administration & dosage ; Methamphetamine/pharmacokinetics ; Mice ; Tetanus Toxoid/administration & dosage ; Tetanus Toxoid/pharmacology
    • Abstract:
      Background and Objectives: We previously reported that an anti-methamphetamine (MA) vaccine attenuated drug-conditioned effects in mice, but it used a carrier protein and adjuvant not available for clinical use. Here we produced a vaccine with the same hapten (succinyl-methamphetamine, SMA) but attached to tetanus toxoid (SMA-TT) and adsorbed to aluminum hydroxide, components approved for use in humans. We then assessed the vaccine's ability to generate anti-MA antibodies, alter acquisition and reinstatement of MA place conditioning, and prevent MA brain penetration.
      Methods: Mice were administered SMA-TT at weeks 0 and 3 and non-vaccinated mice received saline. Anti-MA antibody concentrations were determined at 8 and 12 weeks. Place conditioning began during week 9 in which vaccinated and non-vaccinated mice were divided into groups and conditioned with .5, or 2.0 mg/kg MA. Following acquisition training, mice were extinguished and then a reinstatement test was performed in which mice were administered their original training dose of MA. Separate groups of non-vaccinated and vaccinated mice were administered .5 and 2.0 mg/kg MA and brain MA levels determined.
      Results and Conclusions: Anti-MA antibody levels were elevated at week 8 and remained so through week 12. The SMA-TT vaccine attenuated acquisition and reinstatement of MA place conditioning. Significantly greater proportions of vaccinated mice during acquisition and reinstatement tests showed conditioned place aversion. Moreover, MA brain levels were decreased in vaccinated mice following administration of both doses of MA.
      Scientific Significance: Results support further development of anti-MA vaccines using components approved for use in humans.
      (© American Academy of Addiction Psychiatry.)
    • Grant Information:
      DP1DA033502 United States DA NIDA NIH HHS
    • Accession Number:
      0 (Adjuvants, Immunologic)
      0 (Antibodies)
      0 (Tetanus Toxoid)
      0 (succinyl-methamphetamine-tetanus toxoid vaccine)
      44RAL3456C (Methamphetamine)
      5QB0T2IUN0 (Aluminum Hydroxide)
    • Publication Date:
      Date Created: 20151120 Date Completed: 20160829 Latest Revision: 20191210
    • Publication Date:
      20240104
    • Accession Number:
      10.1111/ajad.12307
    • Accession Number:
      26584468