Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013
Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Maoz Anat, Hicks Martin J, Vallabhjosula Shankar, Synan Michael, Kothari Paresh J, Dyke Jonathan P, Ballon Douglas J, Kaminsky Stephen M, De Bishnu P, Rosenberg Jonathan B, Martinez Diana, Koob George F, Janda Kim D, Crystal Ronald G
Аннотация
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 that 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 <20%, significantly below the 47% threshold required to evoke the subjective 'high' reported in humans.