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Dynamic vaccine blocks relapse to compulsive intake of heroin

Schlosburg, Joel E. ; Vendruscolo, Leandro F. ; Bremer, Paul T. ; Lockner, Jonathan W. ; Wade, Carrie L. ; Nunes, Ashlee A. K. ; Stowe, G. Neil ; Edwards, Scott ; Janda, Kim D. ; Koob, George F.

Proceedings of the National Academy of Sciences - PNAS, 2013-05, Vol.110 (22), p.9036-9041 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
Dynamic vaccine blocks relapse to compulsive intake of heroin
Autor: Schlosburg, Joel E. ; Vendruscolo, Leandro F. ; Bremer, Paul T. ; Lockner, Jonathan W. ; Wade, Carrie L. ; Nunes, Ashlee A. K. ; Stowe, G. Neil ; Edwards, Scott ; Janda, Kim D. ; Koob, George F.
Assuntos: Animals ; Antibodies ; Antibodies - immunology ; Biological Sciences ; Chromatography, Liquid ; Drug therapy ; Heroin ; Heroin - blood ; Heroin - immunology ; Heroin - metabolism ; Heroin dependence ; Heroin Dependence - prevention & control ; Male ; Metabolites ; Morphine ; Morphine - immunology ; Morphine - metabolism ; Morphine Derivatives - blood ; Morphine Derivatives - immunology ; Morphine Derivatives - metabolism ; Motivation ; Opiates ; Opioid analgesics ; Pharmacology ; Psychotropics ; Rats ; Rats, Wistar ; Relapse ; Rodents ; Secondary Prevention ; Self Administration ; Tandem Mass Spectrometry ; Vaccination ; Vaccines ; Vaccines - immunology
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2013-05, Vol.110 (22), p.9036-9041
Notas: http://dx.doi.org/10.1073/pnas.1219159110
Edited by Richard D. Palmiter, University of Washington, Seattle, WA, and approved February 26, 2013 (received for review November 14, 2012)
Author contributions: J.E.S., L.F.V., C.L.W., G.N.S., S.E., K.D.J., and G.F.K. designed research; J.E.S., L.F.V., P.T.B., J.W.L., C.L.W., A.A.K.N., G.N.S., and S.E. performed research; P.T.B., A.A.K.N., G.N.S., and K.D.J. contributed new reagents/analytic tools; J.E.S., P.T.B., J.W.L., A.A.K.N., G.N.S., K.D.J., and G.F.K. analyzed data; and J.E.S. and G.F.K. wrote the paper.
Descrição: 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.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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Dynamic vaccine blocks relapse to compulsive intake of heroin

Schlosburg, Joel E. ; Vendruscolo, Leandro F. ; Bremer, Paul T. ; Lockner, Jonathan W. ; Wade, Carrie L. ; Nunes, Ashlee A. K. ; Stowe, G. Neil ; Edwards, Scott ; Janda, Kim D. ; Koob, George F.

United States: National Academy of Sciences

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