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Dynamic vaccine blocks relapse to compulsive intake of heroin.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2013 May 28; Vol. 110 (22), pp. 9036-41. Date of Electronic Publication: 2013 May 06. - Publication Year :
- 2013
-
Abstract
- Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin's rapid metabolism to 6-acetylmorphine and morphine. We recently developed a "dynamic" vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin's metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin's psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance.
- Subjects :
- Animals
Chromatography, Liquid
Heroin blood
Heroin metabolism
Male
Morphine immunology
Morphine metabolism
Morphine Derivatives blood
Morphine Derivatives immunology
Morphine Derivatives metabolism
Motivation
Rats
Rats, Wistar
Secondary Prevention
Self Administration
Tandem Mass Spectrometry
Antibodies immunology
Heroin immunology
Heroin Dependence prevention & control
Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 110
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 23650354
- Full Text :
- https://doi.org/10.1073/pnas.1219159110