A vaccine against methamphetamine attenuates its behavioral effects in mice
| Autor: | Xiaoyun Y. Shen, Therese A. Kosten, Thomas R. Kosten, Berma M. Kinsey, Frank M. Orson, Angel Y. Lopez |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Amphetamine-Related Disorders Poison control Enzyme-Linked Immunosorbent Assay Motor Activity Toxicology Article Antibodies Methamphetamine Mice Reward Conjugate vaccine Internal medicine medicine Animals Pharmacology (medical) Pharmacology Mice Inbred BALB C Vaccines Behavior Animal Dose-Response Relationship Drug biology business.industry Conditioned place preference Psychiatry and Mental health Dose–response relationship Titer Endocrinology Data Interpretation Statistical Hemocyanins Immunology biology.protein Conditioning Operant Conditioning Central Nervous System Stimulants Female Immunization Carrier Proteins business Keyhole limpet hemocyanin medicine.drug |
| Zdroj: | Drug and Alcohol Dependence. 129:41-48 |
| ISSN: | 0376-8716 |
| DOI: | 10.1016/j.drugalcdep.2012.09.007 |
| Popis: | 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 0.5 mg/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. |
| Databáze: | OpenAIRE |
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