Related Experiment Video
Updated: Jun 2, 2026

A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
Published on: June 18, 2018
Effects of a long-acting mutant bacterial cocaine esterase on acute cocaine toxicity in rats
Gregory T Collins1, Matthew E Zaks, Alyssa R Cunningham
1Department of Pharmacology, 1301 MSRB III, 1150 W. Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA. collinsg@umich.edu
Background:
A longer acting, double mutant bacterial cocaine esterase (CocE T172R/G173Q; DM CocE) has been shown to protect mice from cocaine-induced lethality, inhibit the reinforcing effects of cocaine in rats, and reverse cocaine's cardiovascular effects in rhesus monkeys. The current studies evaluated the effectiveness of DM CocE to protect against, and reverse cocaine's cardiovascular, convulsant, and lethal effects in male and female rats.
Methods:
Pretreatment studies were used to determine the effectiveness and in vivo duration of action for DM CocE to protect rats against the occurrence of cardiovascular changes, convulsion and lethality associated with acute cocaine toxicity. Posttreatment studies were used to evaluate the capacity of DM CocE to rescue rats from the cardiovascular and lethal effects of large doses of cocaine. In addition, male and female rats were studied to determine if there were any potential effects of sex on the capacity of DM CocE to protect against, or reverse acute cocaine toxicity in rats.
Results:
Pretreatment with DM CocE dose-dependently protected rats against cocaine-induced cardiovascular changes, convulsion and lethality, with higher doses active for up to 4h, and shifting cocaine-induced lethality at least 10-fold to the right. In addition to dose-dependently recovering rats from an otherwise lethal dose of cocaine, post-treatment with DM CocE also reversed the cardiovascular effects of cocaine. There were no sex-related differences in the effectiveness of DM CocE to protect against, or reverse acute cocaine toxicity.
Conclusions:
Together, these results support the development of DM CocE for the treatment of acute cocaine toxicity.
Related Concept Videos
CNS Stimulants: Cocaine, Amphetamines and Cannabinoids
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
Toxicity Testing in Animals

