Cocaine hydrochloride in poly(L-lactide) microspheres potentiates effects on the locomotion of rats+

Stress-related effects can often interfere with studies of behavioral pharmacology in animals. This is known to occur where frequent dosing is required as in the study of drugs of abuse. A depot system capable of eliciting a pharmacodynamic response over an extended period would circumvent the need for frequent dosing. Cocaine hydrochloride was incorporated in 4.2 microns median diameter (geometric standard deviation 1.7) poly(L-lactide) microspheres at a concentration of 20% w/w. Seventy percent of the drug load was released in the period from 1-8 h. Studies of the locomotion of rats (n = 10/group) in an open field demonstrated a baseline movement of approximately 0.1 m/h after the intraperitoneal administration of microspheres in saline, or saline alone. Ten milligram of cocaine in saline increased the movement of rats to > 3 m/h for a period of 1 h following injection. The distance travelled by rats after administration of 10 mg of cocaine in microspheres was > 3 m/h for a period up to 6 h. Cocaine delivered in microspheres significantly increased the drug action (0.022 < p < 0.032). Particulate carriers were used to deliver small quantities of drug that overcame the need for multiple dosing of experimental animals to achieve extended behavioral effects.