Viral Transduction of Cocaine Hydrolase
in Brain Reward Centers
Gao Y, Brimijoin S.
Department of Molecular Pharmacology and Experimental Therapeutics,
Mayo Clinic, 200 First St. SW,
Rochester, Minnesota, 55905, USA.
Cell Mol Neurobiol. 2006 May 18;
ABSTRACT1. Site-directed mutagenesis of human plasma butyrylcholinesterase has led to novel hydrolases that rapidly destroy cocaine. We are investigating whether viral gene transfer of such enzymes might reduce addiction liability by blocking cocaine from its sites of action.2. As groundwork for a possible gene therapy, we previously studied adenoviral transduction of cocaine hydrolases in the rat. Systemically injected vectors raised plasma cocaine hydrolase activity greatly, reduced pressor responses to cocaine, and lowered cocaine's tissue burden.3. In the present study, to reduce cocaine's brain access still further, vectors were injected directly into the nucleus accumbens. Six days later, medium sized neurons gained dramatic butyrylcholinesterase activity. Species-selective immunohistochemistry proved that the transgene accounted for this activity.4. Since the transgene product is so efficient with cocaine as a substrate, it is now reasonable to begin testing gene therapy in rodent models of cocaine addiction.Virus therapy
The coke-craving brain
Cocaine and the lonely rat
Freebasing flies go hyperkinetic
01 02 03 04 05 06 07 08 09 10 11 12
13 14 15 16 17 18 19 20 21 22 23 24
The Hedonistic Imperative
MDMA: Utopian Pharmacology
When Is It Best to Take Crack Cocaine?
The Good Drug Guide
The Responsible Parent's Guide To
Healthy Mood Boosters For All The Family