Novel cocaine vaccine linked to a disrupted adenovirus gene transfer vector blocks cocaine psychostimulant and reinforcing effects. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Analysis of Variance
  • Animals
  • Brain
  • Central Nervous System Stimulants
  • Conditioning, Operant
  • Disease Models, Animal
  • Extinction, Psychological
  • Genetic Vectors
  • Haptens
  • Immunoglobulin G
  • Male
  • Methamphetamine
  • Motor Activity
  • Radioimmunoassay
  • Rats
  • Rats, Wistar
  • Self Administration
  • Time Factors
  • Transfer (Psychology)
  • Tritium

MeSH Major

  • Cocaine
  • Cocaine-Related Disorders
  • Dopamine Uptake Inhibitors
  • Reinforcement (Psychology)
  • Vaccination

abstract

  • Immunotherapy is a promising treatment for drug addiction. However, insufficient immune responses to vaccines in most subjects pose a challenge. In this study, we tested the efficacy of a new cocaine vaccine (dAd5GNE) in antagonizing cocaine addiction-related behaviors in rats. This vaccine used a disrupted serotype 5 adenovirus (Ad) gene transfer vector coupled to a third-generation cocaine hapten, termed GNE (6-(2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxamido-hexanoic acid). Three groups of rats were immunized with dAd5GNE. One group was injected with (3)H-cocaine, and radioactivity in the blood and brain was determined. A second group was tested for cocaine-induced locomotor sensitization. A third group was examined for cocaine self-administration, extinction, and reinstatement of responding for cocaine. Antibody titers were determined at various time-points. In each experiment, we added a control group that was immunized with dAd5 without a hapten. The vaccination with dAd5GNE produced long-lasting high titers (>10(5)) of anti-cocaine antibodies in all of the rats. The vaccination inhibited cocaine-induced hyperlocomotor activity and sensitization. Vaccinated rats acquired cocaine self-administration, but they showed less motivation to self-administer cocaine under a progressive-ratio schedule than control rats. When cocaine was not available in a session, control rats exhibited 'extinction burst' responding, whereas vaccinated rats did not. Moreover, when primed with cocaine, vaccinated rats did not reinstate responding, suggesting a blockade of cocaine-seeking behavior. These data strongly suggest that our dAd5GNE vector-based vaccine may be effective in treating cocaine abuse and addiction.

publication date

  • April 2012

has subject area

  • Adenoviridae
  • Analysis of Variance
  • Animals
  • Brain
  • Central Nervous System Stimulants
  • Cocaine
  • Cocaine-Related Disorders
  • Conditioning, Operant
  • Disease Models, Animal
  • Dopamine Uptake Inhibitors
  • Extinction, Psychological
  • Genetic Vectors
  • Haptens
  • Immunoglobulin G
  • Male
  • Methamphetamine
  • Motor Activity
  • Radioimmunoassay
  • Rats
  • Rats, Wistar
  • Reinforcement (Psychology)
  • Self Administration
  • Time Factors
  • Transfer (Psychology)
  • Tritium
  • Vaccination

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3306868

Digital Object Identifier (DOI)

  • 10.1038/npp.2011.200

PubMed ID

  • 21918504

Additional Document Info

start page

  • 1083

end page

  • 1091

volume

  • 37

number

  • 5