title: Altered methamphetamine place conditioning in mice vaccinated with a succinyl-methamphetamine-tetanus-toxoid vaccine.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Results support further development of anti-MA vaccines using components approved for use in humans.
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Houston, Texas.|The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.|Department of Psychology, University of Houston, Houston, Texas.
authors.forename: Colin N
authors.initials: CN
authors.lastname: Haile
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Houston, Texas.|The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.|Department of Psychology, University of Houston, Houston, Texas.
authors.forename: Therese A
authors.initials: TA
authors.lastname: Kosten
authors.affiliation: The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.|Department of Medicine, Immunology Allergy and Rheumatology, Baylor College of Medicine, Houston, Texas.
authors.forename: Xiaoyun Y
authors.initials: XY
authors.lastname: Shen
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Houston, Texas.|The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: O'Malley
authors.affiliation: Department of Psychology, University of Houston, Houston, Texas.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Winoske
authors.affiliation: The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.|Department of Medicine, Immunology Allergy and Rheumatology, Baylor College of Medicine, Houston, Texas.
authors.forename: Berma M
authors.initials: BM
authors.lastname: Kinsey
authors.affiliation: The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.|Department of Medicine, Immunology Allergy and Rheumatology, Baylor College of Medicine, Houston, Texas.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Walvax Biotechnology Co., Ltd, Kunming, Yunnan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: ExperTox, Inc. Deer Park, Deer Park, Texas.
authors.forename: Ernest D
authors.initials: ED
authors.lastname: Lykissa
authors.affiliation: ExperTox, Inc. Deer Park, Deer Park, Texas.
authors.forename: Naga
authors.initials: N
authors.lastname: Naidu
authors.affiliation: ExperTox, Inc. Deer Park, Deer Park, Texas.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Cox
authors.affiliation: The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.|Department of Medicine, Immunology Allergy and Rheumatology, Baylor College of Medicine, Houston, Texas.
authors.forename: Reetakshi
authors.initials: R
authors.lastname: Arora
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Houston, Texas.|The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
authors.affiliation: The Michael E DeBakey Veteran's Affairs Medical Center, Houston, Texas.|Department of Medicine, Immunology Allergy and Rheumatology, Baylor College of Medicine, Houston, Texas.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Orson
mesh_terms: D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D019969:Amphetamine-Related Disorders / Q000517:prevention & control*; D000818:Animals; D000906:Antibodies / Q000097:blood; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects*; D005260:Female; D008694:Methamphetamine / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D013745:Tetanus Toxoid; C000610125:succinyl-methamphetamine-tetanus toxoid vaccine; D008694:Methamphetamine; D000536:Aluminum Hydroxide