PT  - JOURNAL ARTICLE
AU  - John R. Smethells
AU  - Natashia Swalve
AU  - Stephen Brimijoin
AU  - Yang Gao
AU  - Robin J. Parks
AU  - Adam Greer
AU  - Marilyn E. Carroll
TI  - Long-Term Blockade of Cocaine Self-Administration and Locomotor Activation in Rats by an Adenoviral Vector–Delivered Cocaine Hydrolase
AID  - 10.1124/jpet.116.232504
DP  - 2016 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 375--381
VI  - 357
IP  - 2
4099  - http://jpet.aspetjournals.org/content/357/2/375.short
4100  - http://jpet.aspetjournals.org/content/357/2/375.full
SO  - J Pharmacol Exp Ther2016 May 01; 357
AB  - A promising approach in treating cocaine abuse is to metabolize cocaine in the blood using a mutated butyrylcholinesterase (BChE) that functions as a cocaine hydrolase (CocH). In rats, a helper-dependent adenoviral (hdAD) vector–mediated delivery of CocH abolished ongoing cocaine use and cocaine-primed reinstatement of drug-seeking for several months. This enzyme also metabolizes ghrelin, an effect that may be beneficial in maintaining healthy weights. The effect of a single hdAD-CocH vector injection was examined in rats on measures of anxiety, body weight, cocaine self-administration, and cocaine-induced locomotor activity. To examine anxiety, periadolescent rats were tested in an elevated-plus maze. Weight gain was then examined under four rodent diets. Ten months after CocH-injection, adult rats were trained to self-administer cocaine intravenously and, subsequently, cocaine-induced locomotion was tested. Viral gene transfer produced sustained plasma levels of CocH for over 13 months of testing. CocH-treated rats did not differ from controls in measures of anxiety, and only showed a transient reduction in weight gain during the first 3 weeks postinjection. However, CocH-treated rats were insensitive to cocaine. At 10 months postinjection, none of the CocH-treated rats initiated cocaine self-administration, unlike 90% of the control rats. At 13 months postinjection, CocH-treated rats showed no cocaine-induced locomotion, whereas control rats showed a dose-dependent enhancement of locomotion. CocH vector produced a long-term blockade of the rewarding and behavioral effects of cocaine in rats, emphasizing its role as a promising therapeutic intervention in cocaine abuse.