Animal Models and the Development of Vaccines to Treat Substance Use Disorders

Ohia-Nwoko, Odochi; Kosten, Therese A.; Haile, Colin N.

doi:10.1016/bs.irn.2016.02.009

Cited by 32 publications

(28 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Immunopharmacotherapy, specifically through active immunization, has been utilized as a method for the sequestration of drug molecules from the brain and for the reduction of drug effects. By eliciting high-affinity drug-specific antibodies, anti-drug vaccines have been developed as potential therapeutics (see (Kosten and Domingo, 2013; Ohia-Nwoko et al, 2016; Skolnick, 2015; Zalewska-Kaszubska, 2015) for review), for psychomotor stimulants such as MA and cocaine (Kosten et al, 2014) and even recently emerged designer cathinones, such as alpha-pyrrolidinopentiophenone and 3,4-methylenedioxypyrovalerone (Nguyen et al, 2016c). Multiple reports followed a seminal demonstration that an anti-cocaine vaccine produced an attenuation of cocaine-stimulated locomotor increases in male Wistar rats (Carrera et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Effective active vaccination against methamphetamine in female rats

Nguyen

Bremer

Hwang

et al. 2017

Drug and Alcohol Dependence

View full text Add to dashboard Cite

Background Immunotherapies directed against methamphetamine (MA) abuse have shown success in rodent models, however only a limited number of studies have investigated active vaccination in female mice and none in female rats. It is critical to determine if potential immunotherapeutic strategies generalize across sex, particularly for drugs that may produce significant sex-differences on behavioral or physiological endpoints. Methods Female Wistar rats were initially vaccinated with keyhole-limpet hemocyanin (KLH) or an anti-methamphetamine-KLH conjugate (MH6-KLH) three times over five weeks and implanted with radiotelemetry devices to assess locomotor activity and body temperature responses to MA. Rats were first exposed to MA via vapor inhalation (100mg/mL in propylene glycol) and then by injection (0.25–1.0 mg/kg, i.p.) and vapor after a final vaccine boost. Results The MH6-KLH vaccine generated an increase in antibody titers across the initial 6-week, 3 immunization protocol and a restoration of titer after a week 14 booster. Locomotor stimulation induced by 0.25 mg/kg MA, i.p, in the KLH group was prevented in the MH6-KLH group. MH6-KLH animals also exhibited an attenuated locomotor stimulation produced by 0.5 mg/kg MA, i.p. No group differences in locomotion induced by vapor inhalation of MA were observed and body temperature was not differentially affected by MA across the groups, most likely because vapor inhalation of MA that produced similar locomotor stimulation resulted in ~10-fold higher plasma MA levels. Conclusions This study confirms the efficacy of the MH6-KLH vaccine in attenuating the effects of MA in female rats.

show abstract

Section: Introductionmentioning

confidence: 99%

Effective active vaccination against methamphetamine in female rats

Nguyen

Bremer

Hwang

et al. 2017

Drug and Alcohol Dependence

View full text Add to dashboard Cite

show abstract

“…Anti-drug vaccination alters the effects of many drugs of abuse (Bremer and Janda, 2017;Lockner and Janda, 2013;Ohia-Nwoko et al, 2016); vaccines against cocaine (Haney et al, 2010;Kosten et al, 2002;Martell et al, 2009) and nicotine (Cornuz et al, 2008;Hatsukami et al, 2011) have advanced to clinical trials. Initial studies by Pravetoni and colleagues showed that an oxycodone-specific vaccine could induce antibodies capable of sequestering oxycodone in the blood and lowering brain penetration of oxycodone in rats (Pravetoni et al, 2012;Pravetoni et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Prophylactic vaccination protects against the development of oxycodone self-administration

Nguyen

Hwang

Grant

et al. 2017

Preprint

View full text Add to dashboard Cite

Abuse of prescription opioids is a growing public health crisis in the United States, with drug overdose deaths increasing dramatically over the past 15 years. Few preclinical studies exist on the reinforcing effects of oxycodone or on the development of therapies for oxycodone abuse. This study was conducted to determine if immunopharmacotherapy directed against oxycodone would be capable of altering oxycodone-induced antinociception and intravenous self-administration. Male Wistar rats were administered a small-molecule immunoconjugate vaccine (Oxy-TT) or the control carrier protein, tetanus toxoid (TT), and trained to intravenously self-administer oxycodone (0.06 or 0.15 mg/kg/infusion). Brain oxycodone concentrations were 50% lower in Oxy-TT rats compared to TT rats 30 minutes after injection (1 mg/kg, s.c.) whereas plasma oxycodone was 15-fold higher from drug sequestration by circulating antibodies. Oxy-TT rats were also less sensitive to 1-2 mg/kg, s.c. oxycodone on a hot water nociception assay. Half of the Oxy-TT rats failed to acquire IVSA under the 0.06 mg/kg/infusion training dose. Oxycodone self-administration of Oxy-TT rats trained on 0.15 mg/kg/infusion was higher than controls; however under progressive ratio (PR) conditions the Oxy-TT rats decreased their oxycodone intake, unlike TT controls. These data demonstrate that active vaccination provides protection against the antinociceptive and reinforcing effects of oxycodone. Anti-drug vaccines may entirely prevent repeated use in some individuals who otherwise would become addicted. Vaccination may also reduce dependence in those who become addicted and therefore facilitate the effects of other therapeutic interventions which increase the difficulty of drug use or incentivize other behaviors.

show abstract

“…The reader is referred to recent reviews and articles on these topics [161–164]. Overall, the logic of the vaccine approaches is to produce a sufficient host immune response to a major drug of interest (e.g., cocaine or a specific μ-agonist), such that the actual blood concentrations of free drug are decreased sufficiently that the CNS-mediated effects of the drug are decreased.…”

Section: Current Research Goalsmentioning

confidence: 99%

Medications for substance use disorders (SUD): emerging approaches

Butelman

Kreek

2017

Expert Opinion on Emerging Drugs

View full text Add to dashboard Cite

Introduction: Substance use disorders are a group of chronic relapsing disorders of the brain, which have massive public health and societal impact. In some disorders (e.g., heroin / prescription opioid addictions) approved medications have a major long-term benefit. For other substances (e.g., cocaine, amphetamines and cannabis) there are no approved medications, and for alcohol there are approved treatments, which are not in wide usage. Approved treatments for tobacco use disorders are available, and novel medications are also under study. Areas covered: Medication-based approaches which are in advanced preclinical stages, or which have reached proof-of concept clinical laboratory studies, as well as clinical trials. Expert opinion: Current challenges involve optimizing translation between preclinical and clinical development, and between clinical laboratory studies to therapeutic clinical trials. Comorbidities including depression or anxiety are challenges for study design and analysis. Improved pharmacogenomics, biomarker and phenotyping approaches are areas of interest. Pharmacological mechanisms currently under investigation include modulation of glutamatergic, GABA, vasopressin and κ-receptor function, as well as inhibition of monoamine re-uptake. Other factors that affect potential market size for emerging medications include stigma, availability of treatment settings, adoption by clinicians, and the prevalence of persons with SUD who are not actively treatment-seeking.

show abstract

Animal Models and the Development of Vaccines to Treat Substance Use Disorders

Cited by 32 publications

References 122 publications

Effective active vaccination against methamphetamine in female rats

Effective active vaccination against methamphetamine in female rats

Prophylactic vaccination protects against the development of oxycodone self-administration

Medications for substance use disorders (SUD): emerging approaches

Contact Info

Product

Resources

About