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

Abstract

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. 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 mu m 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 irt 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 experimental animals to achieve extended behavioral effects