combined cocaine hydrolase gene transfer and anti-cocaine vaccine synergistically block cocaine-induced locomotion结合可卡因水解酶基因转移和anti-cocaine疫苗阻止cocaine-induced协同运动.pdfVIP

Combined Cocaine Hydrolase Gene Transfer and Anti- Cocaine Vaccine Synergistically Block Cocaine-Induced Locomotion 1 1 1 2 2 Marilyn E. Carroll , Natalie E. Zlebnik , Justin J. Anker , Thomas R. Kosten , Frank M. Orson , 2 2 3 4 4 Xiaoyun Shen , Berma Kinsey , Robin J. Parks , Yang Gao , Stephen Brimijoin * 1 Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, United States of America, 2 Departments of Medicine, Psychiatry Neuroscience, and Pathology Immunology, Baylor College of Medicine and Veterans Administration Medical Center, Houston, Texas, United States of America, 3 Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario Canada, 4 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, United States of America Abstract Mice and rats were tested for reduced sensitivity to cocaine-induced hyper-locomotion after pretreatment with anti-cocaine antibody or cocaine hydrolase (CocH) derived from human butyrylcholinesterase (BChE). In Balb/c mice, direct i.p. injection of CocH protein (1 mg/kg) had no effect on spontaneous locomotion, but it suppressed responses to i.p. cocaine up to 80 mg/kg. When CocH was injected i.p. along with a murine cocaine antiserum that also did not affect spontaneous locomotion, there was no response to any cocaine dose. This suppression of locomotor activity required active enzyme, as it was lost after pretreatment with iso-OMPA, a selective BChE inhibitor. Comparable results were obtained in rats that developed high levels of CocH by gene transfer with helper-dependent a