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Effects of a methamphetamine vaccine, IXT-v100, on methamphetamine-related behaviors

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Abstract

Rationale:

Vaccines have been developed as a potential treatment for methamphetamine (meth) use disorder (MUD). Immunization with the meth vaccine IXT-v100 has previously been shown to elicit antibodies with high affinity for meth and thus may be an effective treatment for MUD.

Objectives:

These studies were designed to determine the efficacy of IXT-v100 on meth-taking and meth-seeking behaviors in rats.

Methods:

In the acquisition and maintenance study, male and female rats were trained to self-administer meth (0.06 mg/kg/infusion) over an 8-week period following vaccination. In the last 4 weeks, the dose of meth was increased or decreased each week. To assess meth-seeking behavior, the meth-primed reactivity model was used. Rats were trained to self-administer meth for 5 weeks, followed by a 5-week or 11-week forced abstinence period during which the animals were vaccinated. Rats were then placed back into the self-administration chamber immediately after being injected with meth (1 mg/kg, i.p.) but did not receive meth during the session. Responses were recorded and used as a measure of meth seeking.

Results:

Results from the acquisition and maintenance study in Wistar rats show that vaccination with IXT-v100 adjuvanted with glucopyranosyl lipid A stable emulsion decreases the percentage of animals that will self-administer a moderate level of meth. In the meth-primed reactivity studies, results from males showed that vaccination significantly attenuates meth-seeking behavior.

Conclusion:

Together, these results suggest vaccination with IXT-v100 may be effective at decreasing meth-taking and meth-seeking behaviors in humans suffering with MUD.

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Funding

This work was supported by the National Institute on Drug Abuse of the National Institutes of Health (grant number U01DA035511). The grant was awarded to InterveXion Therapeutic with MWS and SMO as co-PD/PI.

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Authors and Affiliations

  1. Department of Pharmacology, Toxicology & Neuroscience, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA

    Courtney M Keller, Glenn F Guerin & Nicholas E Goeders

  2. Regis University School of Pharmacy, 3333 Regis Boulevard, Denver, CO, 80221, USA

    Allyson L Spence

  3. InterveXion Therapeutics, LLC, 4301 W. Markham St. #831, Little Rock, AR, 72205, USA

    Misty W Stevens & S. Michael Owens

  4. Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 W. Markham St. #611, Little Rock, AR, 72205, USA

    S. Michael Owens

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  1. Courtney M Keller
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  2. Allyson L Spence
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  3. Misty W Stevens
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Correspondence to Courtney M Keller.

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The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of interest

SMO has financial and fiduciary interests in InterveXion Therapeutic LLC (Little Rock, AR), a pharmaceutical company. UAMS has licensed intellectual property developed by SMO to InterveXion Therapeutics LLC. MWS is Chief Operating Officer of InterveXion Therapeutics which had a role in the study design, interpretation, and review of the manuscript. CMK, ALS, GFG, and NEG have no conflicts of interest to declare.

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Keller, C.M., Spence, A.L., Stevens, M.W. et al. Effects of a methamphetamine vaccine, IXT-v100, on methamphetamine-related behaviors. Psychopharmacology 237, 655–667 (2020). https://doi.org/10.1007/s00213-019-05399-6

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  • DOI: https://doi.org/10.1007/s00213-019-05399-6

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