Novel cocaine vaccine linked to a disrupted adenovirus gene transfer vector blocks cocaine psychostimulant and reinforcing effects

Sunmee Wee, Martin J. Hicks, Bishnu P. De, Jonathan B. Rosenberg, Amira Y. Moreno, Stephen M. Kaminsky, Kim D. Janda, Ronald Crystal, George F. Koob

Research output: Contribution to journalArticle

54 Citations (Scopus)

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 3H-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.

Original languageEnglish
Pages (from-to)1083-1091
Number of pages9
JournalNeuropsychopharmacology
Volume37
Issue number5
DOIs
Publication statusPublished - 1 Apr 2012
Externally publishedYes

Fingerprint

Cocaine
Adenoviridae
Vaccines
Genes
Cocaine-Related Disorders
Self Administration
Haptens
Transfer (Psychology)
Vaccination
Immunotherapy
Radioactivity
Substance-Related Disorders
Motivation
Anti-Idiotypic Antibodies
Appointments and Schedules

Keywords

  • cocaine
  • locomotor activity
  • rats
  • reinstatement
  • self-administration
  • vaccine

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Wee, S., Hicks, M. J., De, B. P., Rosenberg, J. B., Moreno, A. Y., Kaminsky, S. M., ... Koob, G. F. (2012). Novel cocaine vaccine linked to a disrupted adenovirus gene transfer vector blocks cocaine psychostimulant and reinforcing effects. Neuropsychopharmacology, 37(5), 1083-1091. https://doi.org/10.1038/npp.2011.200

Novel cocaine vaccine linked to a disrupted adenovirus gene transfer vector blocks cocaine psychostimulant and reinforcing effects. / Wee, Sunmee; Hicks, Martin J.; De, Bishnu P.; Rosenberg, Jonathan B.; Moreno, Amira Y.; Kaminsky, Stephen M.; Janda, Kim D.; Crystal, Ronald; Koob, George F.

In: Neuropsychopharmacology, Vol. 37, No. 5, 01.04.2012, p. 1083-1091.

Research output: Contribution to journalArticle

Wee, Sunmee ; Hicks, Martin J. ; De, Bishnu P. ; Rosenberg, Jonathan B. ; Moreno, Amira Y. ; Kaminsky, Stephen M. ; Janda, Kim D. ; Crystal, Ronald ; Koob, George F. / Novel cocaine vaccine linked to a disrupted adenovirus gene transfer vector blocks cocaine psychostimulant and reinforcing effects. In: Neuropsychopharmacology. 2012 ; Vol. 37, No. 5. pp. 1083-1091.
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