A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats

Li, Qianqian; Sun, Chengyu; Luo, Yunping; Xue, Yan-Xue; Meng, Shi-Qiu; Xu, Lingzhi; Chen, Na; Deng, Jiahui; Zhai, Haifeng; Kosten, Thomas R.; Shi, Jie; Lü, Lin; Sun, Hongqiang

doi:10.1093/ijnp/pyu093

Cited by 24 publications

(22 citation statements)

References 53 publications

(81 reference statements)

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“…The rodent model used in this experiment can be adapted to the study of other novel treatments for opioid abuse. These include BUP implants (Ling et al, 2010;Rosenthal et al, 2013), BUP-gabapentin combination therapy (Sanders et al, 2013), memantine-naltrexone therapy (Bisaga et al, 2011(Bisaga et al, , 2014, slow-release morphine treatment (Jegu et al, 2011), herbal and plant remedies (Gao et al, 2014;Tabatabai et al, 2014), as well as potential immunotherapies including conjugate morphine-heroin vaccines (Li et al, 2011(Li et al, , 2015. Given the abundance of studies on therapeutic intervention, as well as epidemiologic data indicating escalating levels of opioid abuse, additional investigations into existing and novel treatments are warranted.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement

Santoro

Carrion

Patel

et al. 2017

Neuropsychopharmacol

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Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic efficacy, whereas these posttreatment sex differences contribute to clinical treatment failure more commonly experienced by the former.

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Section: Discussionmentioning

confidence: 99%

Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement

Santoro

Carrion

Patel

et al. 2017

Neuropsychopharmacol

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“…Therapeutic vaccines for heroin and prescription opioid abuse have shown efficacy in a wide range of preclinical models, demonstrating that immunization can reduce opioid distribution to the brain and attenuate opioid-related behaviors including self-administration, locomotor activation, and analgesia in mice, rats, and non-human primates (Bonese et al, 1974;Anton and Leff, 2006;Li et al, 2011Li et al, , 2014Stowe et al, 2011;Pravetoni et al, 2012bPravetoni et al, ,c, 2013Pravetoni et al, , 2014aKosten et al, 2013;Raleigh et al, 2013Raleigh et al, , 2014Schlosburg et al, 2013;Laudenbach et al, 2015;Bremer et al, 2017). However, vaccine efficacy is often tested in animals using immunization protocols involving routes of administration (e.g., intraperitoneal) and adjuvants (e.g., Freund's complete adjuvant) that are not used in humans, or at opioid doses that are suitable for the animal models chosen but are at the lower end of the range that may be abused by humans.…”

Section: Introductionmentioning

confidence: 99%

Opioid Dose- and Route-Dependent Efficacy of Oxycodone and Heroin Vaccines in Rats

Raleigh

Laudenbach

Baruffaldi

et al. 2018

J Pharmacol Exp Ther

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Heroin and oxycodone abuse occurs over a wide range of drug doses and by various routes of administration characterized by differing rates of drug absorption. The current study addressed the efficacy of a heroin vaccine [morphine hapten conjugated to keyhole limpet hemocyanin (M-KLH)] or oxycodone vaccine [oxycodone hapten conjugated to keyhole limpet hemocyanin (OXY-KLH)] for reducing drug distribution to brain after intravenous heroin or oxycodone, or subcutaneous oxycodone. Rats immunized with M-KLH or keyhole limpet hemocyanin (KLH) control received an intravenous bolus dose of 0.26 or 2.6 mg/kg heroin. Vaccination with M-KLH increased retention of heroin and its active metabolites 6-acetylmorphine (6-AM) and morphine in plasma compared with KLH controls, and reduced total opioid (heroin 1 6-AM 1 morphine) distribution to brain but only at the lower heroin dose. Immunization also protected against respiratory depression at the lower heroin dose. Rats immunized with OXY-KLH or KLH control received 0.22 or 2.2 mg/kg oxycodone intravenously, the molar equivalent of the heroin doses. Immunization with OXY-KLH significantly reduced oxycodone distribution to brain after either oxycodone dose, although the magnitude of effect of immunization at the higher oxycodone dose was small (12%). By contrast, vaccination with OXY-KLH was more effective when oxycodone was administered subcutaneously rather than intravenously, reducing oxycodone distribution to brain by 44% after an oxycodone dose of 2.3 mg/kg. Vaccination also reduced oxycodone-induced antinociception. These data suggest that the efficacy of OXY-KLH and M-KLH opioid vaccines is highly dependent upon opioid dose and route of administration.

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“…Por su parte, Li y colaboradores emplearon una vacuna conjugada en la que se usó como hapteno a la 6-glutarilmorfina unida a KLH, que atenuó la conducta y los efectos psicoactivos de la heroína en ratas; además, se incrementó la concentración de anticuerpos específi-cos para morfina y heroína que no tuvieron especificidad de reconocimiento por otras sustancias opioides, tales como buprenorfina, metadona, naloxona, naltrexona, nalorfina o codeína (Li et al, 2011;Li et al, 2015). Esta propiedad es relevante debido a que estos opioides pueden usarse como terapia farmacológica complementaria a la adicción y se usan de manera amplia como analgésicos.…”

Section: Vacunas Para Morfina Y Heroínaunclassified

El estado actual de las vacunas contra las drogas

Matus-Ortega¹,

Nieves²,

Barbosa-Méndez³

et al. 2017

RIIAD

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Introducción: por lo común, la adicción a las drogas se trata con psicoterapia y farmacología que evita la unión de las sustancias psicoactivas a receptores específicos en el cerebro. El resultado de estos tratamientos no ha sido del todo satisfactorio, por lo que el desarrollo de terapias más eficaces representa un reto constante para tratar las adicciones. Una alternativa a la farmacología antiadictiva es la vacunación activa dirigida contra las sustancias de abuso. Objetivo: esta revisión reúne la información disponible sobre los fundamentos y avances científicos en la generación de una terapia inmunológica, que coadyuve al tratamiento de la adicción a sustancias como la heroína-morfina, la cocaína, la nicotina y la anfetamina. Método: se consideraron los reportes científicos disponibles en PubMed –de 2005 a abril de 2017–, sobre los fundamentos, la metodología empleada, los estudios preclínicos y clínicos, y los resultados obtenidos en dichas investigaciones para generar vacunas contra las drogas. Resultados: las vacunas lograron mitigar los efectos producidos por las sustancias en los estudios preclínicos en modelos de estudio en animales; sin embargo, con pacientes humanos los resultados no han sido del todo satisfactorios. Discusión y conclusiones a pesar de los esfuerzos realizados por diferentes grupos de investigación y compañías farmacéuticas para generar vacunas terapéuticas contra el uso de diferentes drogas, ninguna ha alcanzado la fase III de estudios clínicos. En la actualidad, se continúa con los esfuerzos para lograr que las vacunas contra las adicciones alcancen su máxima eficiencia y eficacia, y contribuyan al tratamiento de la adicción a las drogas.

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A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats

Cited by 24 publications

References 53 publications

Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement

Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement

Opioid Dose- and Route-Dependent Efficacy of Oxycodone and Heroin Vaccines in Rats

El estado actual de las vacunas contra las drogas

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