title: Dynamic vaccine blocks relapse to compulsive intake of heroin.
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.
authors: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA. schlos@scripps.edu
authors: Joel E
authors: JE
authors: Schlosburg
authors: Leandro F
authors: LF
authors: Vendruscolo
authors: Paul T
authors: PT
authors: Bremer
authors: Jonathan W
authors: JW
authors: Lockner
authors: Carrie L
authors: CL
authors: Wade
authors: Ashlee A K
authors: AA
authors: Nunes
authors: G Neil
authors: GN
authors: Stowe
authors: Scott
authors: S
authors: Edwards
authors: Kim D
authors: KD
authors: Janda
authors: George F
authors: GF
authors: Koob
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D002853:Chromatography, Liquid; D003932:Heroin / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006556:Heroin Dependence / Q000517:prevention & control*; D008297:Male; D009020:Morphine / Q000276:immunology / Q000378:metabolism; D009022:Morphine Derivatives / Q000097:blood / Q000276:immunology / Q000378:metabolism; D009042:Motivation; D051381:Rats; D017208:Rats, Wistar; D055502:Secondary Prevention; D012646:Self Administration; D053719:Tandem Mass Spectrometry; D014612:Vaccines / Q000276:immunology*
chemical_list: D000906:Antibodies; D009022:Morphine Derivatives; D014612:Vaccines; D003932:Heroin; D009020:Morphine; C026979:6-O-monoacetylmorphine
keywords: antinociception; immunotherapy; progressive ratio
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