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. abuse. A depot system c apable 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 devia tion 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 de monstrated a baseline movement of approximately 0.1 m/h after the intr aperitoneal 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 travelle d 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 sign ificantly increased the drug action (0.022 < p < 0.032). Particulate c arriers were used to deliver small quantities of drug that overcame th e need for multiple dosing of experimental experimental animals to ach ieve extended behavioral effects.