Citation

Maoz A, Hicks MJ, Vallabhjosula S, Synan M, Kothari PJ, Dyke JP, Ballon DJ, Kaminsky SM, De BP, Rosenberg JB, Martinez D, Koob GF, Janda KD, Crystal RG. Neuropsychopharmacology 2013; 38(11): 2170-2178.

Affiliation

1] Division of Nuclear Medicine and Molecular Imaging, New York, New York, USA [2] Department of Radiology, Citigroup Biomedical Imaging Center, New York, New York, USA.

Copyright

(Copyright © 2013, Nature Publishing Group)

DOI

10.1038/npp.2013.114

PMID

23660705

Abstract

Cocaine addiction is a major problem for which there is no approved pharmacotherapy. We have developed a vaccine to cocaine (dAd5GNE), based on the cocaine analog GNE linked to the capsid proteins of a serotype 5 adenovirus, designed to evoke anti-cocaine antibodies which sequester cocaine in the blood, preventing access to the CNS. To assess the efficacy of dAd5GNE in a large animal model, positron emission tomography (PET) and the radiotracer [(11)C]PE2I were used to measure cocaine occupancy of the dopamine transporter (DAT) in nonhuman primates. Repeat administration of dAd5GNE induced high anti-cocaine titers. Before vaccination, cocaine displaced PE2I from DAT in the caudate and putamen, resulting in 62±4% cocaine occupancy. In contrast, dAd5GNE vaccinated animals showed reduced cocaine occupancy such that when anti-cocaine titers were >4 × 10(5), the cocaine occupancy was reduced to levels of less than 20%, significantly below the 47% threshold required to evoke the subjective "high" reported in humans.Neuropsychopharmacology accepted article preview online, 10 May 2013; doi:10.1038/npp.2013.114.

Language: en